Methods and compositions for heat shock protein mediated immunotherapy of melanoma

ABSTRACT

The present invention relates to immunotherapeutic compositions comprising an effective amount of a molecular chaperone such as a heat shock protein, preferably hsp70, non-covalently bound to one or more javelinized melanoma antigens and to methods of using the immunotherapeutic compositions to induce an immune response against melanoma in a subject. The immunotherapeutic composition may contain one or more heat shock proteins, such as one or more of hsp70, hsp90, gp96, BiP, and hsp40, and may contain one or more javelinized melanoma antigens.

1. INTRODUCTION

[0001] The present invention relates to novel compositions and methodsfor treating or preventing malignant melanoma, whereby a subject isimmunized with a composition comprising one or more melanoma antigenbound, via a molecular tether referred to as a “javelin”, to a heatshock protein.

2. BACKGROUND OF THE INVENTION 2.1 Melanoma

[0002] Malignant melanoma is the most serious form of skin cancer,accounting for two percent of all cancers. It is currently the eighthmost common cancer in the United States, with about 47,000 new cases peryear of melanoma in the United States alone.

[0003] The American Joint Committee on Cancer (“AJCC”) has developed astaging system (currently under revision) which classifies melanomaaccording to thickness (depth) of the tumor and the extent to which ithas spread. The AJCC has proposed a new set of criteria which alsoconsider, among other things, whether or not a melanoma is ulcerated andthe number, rather than the gross dimensions, of metastatic lymph nodes(Balch et al., 2000, Cancer 88(6):1484-1491).

[0004] Surgery can be curative for the earliest stages of melanoma, andwide excision of a primary cutaneous melanoma is associated with a10-year cure rate of 85 percent when the tumor's depth is less than 1.5mm (AJCC Stage I). However, according to Barth and Morton, 1995, Cancer15 (2 Suppl):726-734, recurrence will occur in 50 percent of patientswith deep (>4 mm) primary melanomas, 60-85 percent of patients withregional lymph node metastases (AJCC Stage III) and 95 percent ofpatients with distant metastases (AJCC Stage IV). Even melanoma patientswith AJCC Stage III or Stage IV disease who are free of detectabledisease or have minimal disease have a less than 50% chance of survivingfive years with currently available therapy. (Parker et al., 1997,Cancer Statistics 47:5-27, 1997; Houghton, 1992, Cutaneous Melanoma, 2ed., J. B. Lippincott, pp. 499-508; Sirott et al., 1993, Cancer72:3091-3098). Therefore, research efforts have been directed towarddeveloping adjuvant therapies for melanoma.

[0005] According to Agarwala and Kirkwood, 2000, Forum (Genova)10(3):230-239, although a number of agents have been tested for theadjuvant therapy of high risk melanoma, the only one to demonstrate animprovement in relapse-free and overall survival is interferon-alpha 2b,administered at maximally tolerated doses. Interferon gamma has beenobserved to exert certain effects which are similar to those produced byinterferon alpha on melanoma cells in culture (Heninger et al., 2000,Inflamm. Res. 49(8):393-397), and clinical trials are under way in whicha retroviral vector carrying an interferon gamma gene is being deliveredinto the tumors of patients with metastatic melanoma (Fujii et al.,2000, Cancer Gene Ther. 7(9):1220-1230).

2.2 Melanoma Antigens

[0006] Melanoma antigens, including gangliosides such as GM2 and GD3 andvarious peptides, have been identified that can act as specific targetsfor immune recognition and destruction of melanoma cells (Cebon et al.,1997, Austral. J. Dermatol. 38(Suppl 1):S66-S72).

[0007] The development of effective vaccines or immunotherapies formelanoma is dependent on the generation of protective immune responsesto melanoma antigens.

[0008] Peptide antigens on the melanoma cell surface in association withHuman Leukocyte Antigen (“HLA”) molecules have been identified which arerecognized by cytotoxic lymphocytes (Cebon et al., 1997, Austral. J.Dermatol. 38(Suppl 1):S66-S72). Examples of specific antigens includeMAGE proteins, tyrosinase, tyrosinase related proteins 1 and 2 (“TRP-1”and “TRP-2”), MelanA/MART-1, gp100, NY-ES01, BAGE-, GAGE-1/2 and others(see Dalerba et al., 1998, Int. J. Cancer 77(2 :200-204; Boel et al.,1995, Immunity 2:167-175). There have been a number of reports relatingto the evaluation of melanoma associated peptide-based vaccines as atreatment modality (Rosenberg et al., 1998, Nature Medicine 4:321-327;Lewis et al., 2000, Int. J. Cancer 87:391-398; Jaeger et al., 1996, Int.J. Cancer 66:162-169; Nestle et al., 1998, Nature Medicine 4:328-332).

[0009] MAGE (Melanoma Antigen GEnes) proteins are encoded by a family ofat least twenty-one related genes, including MAGE-1 to −12 (now namedMAGE-A1-A12, MAGE-B1 to B4, and MAGE-C1), and four newly identified MAGEgenes, namely MAGE-B5, MAGE-B6, MAGE-C2 and MAGE-C3 (Lucas et al., 2000,Int. J. Cancer 87(1):55-60). Genes of this family are expressed invarious tumors of different histological types but are silent in normaltissues, with the exception of male germ line cells (which lack HLAexpression) and placenta. Although many of these genes are selectivelyexpressed in melanoma cells, Gibbs et al., 2000, Melanoma Res.10(3):259-264 reports that MAGE-12 and MAGE-6 were expressed at higherfrequencies (74 percent and 64 percent, respectively) than the otherMAGE genes.

[0010] Tyrosinase is the rate-limiting enzyme in melanin synthesis andis a melanoma associated antigen that is recognized, in anHLA-restricted manner, by CD4+ and CD8+ T lymphocytes (Fetsch et al.,2000, Cancer 90(4:252-257). Tyrosinase-derived peptides are currentlybeing utilized as targets for T cells in several immunotherapy protocolsfor metastatic malignant melanoma at the National Institutes ofHealth/National Cancer Institute of the United States (Id.).

[0011] In addition to tyrosinase, two tyrosinase family antigensassociated with melanoma have been identified, known as Tyrosine RelatedProteins 1 and 2 (“TRP-1 and TRP-2”). Immunization of mice with TRP-1(Vuayasaradhi and Houghton, 1991, Int. J. Cancer 47:298-303; TRP-1 isalso referred to in the literature as gp75 or the brown locus protein)has been observed to induce tumor immunity and autoimmunity (manifestedas depigmentation) that is mediated by autoantibodies (Bowne et al.,1999, J. Exp. Med. 190(11):1717-1722, citing Weber et al., 1998, J.Clin. Invest. 102:1258-1264; Hara et al., 1995, J. Exp. Med.182:1609-1614; Nafzger et al., 1996, Proc. Natl. Acad. Sci. U.S.A.93:14809-14814; and Clynes et al., 1998, Proc. Natl. Acad. Sci. U.S.A.95:652-656).

[0012] TRP-2 (also known as the slaty locus protein) has been found tofrequently be expressed in melanoma cells (Noppen et al., 2000, Int. J.Cancer 87(2):241-246). Seven HLA-A*0201-restricted TRP-2 peptides werefound to bind to HLA-A*0201 binding motifs by computer-assisted reverseimmunology; of these seven, two, TRP-2(360-368) and TRP-2(476-484)induced specific CD8+ cytotoxic T lymphocytes (Id.). An additionalepitope-containing peptide, TRP-2(288-296), was identified by Sun etal., 2000, Int. J. Cancer 87(3):399-404.

[0013] MART-1 (Melanoma Antigen Recognized by T-Cells-1) is a melanocytedifferentiation antigen (U.S. Pat. No. 5,874,560 by Kawakami,Brinckerhoffet al., 1999, Int. J. Cancer 83(3):326-334; Zarour et al.,2000, Proc. Natl. Acad. Sci. U.S.A. 97(1):400-405; Kawakami et al.,1994, Proc. Natl. Acad. Sci. U.S.A. 91:6458-6462; Castelli et al., 1995,J. Exp. Med. 181(1):363-368). The human Melan-A/MART-1 gene encodes anHLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8+cytotoxic T lymphocytes, but Zarour et al., 2000, Proc. Natl. Acad. Sci.U.S.A. 97(1):400-405 have identified a peptide fragment of MART-1 whichis HLA-DR4 presented and recognized by CD4+ T lymphocytes.

[0014] The gp100 gene was localized to chromosome 12p-q21 and encodes aglycoprotein, recognized by monoclonal antibody HMB-45, that is mainlylocalized in the membrane and filamentous matrix of pre-melanosomes,suggesting that it may be involved in melanin synthesis. Gp100 isrecognized as a melanoma-associated antigen, and gp 100 mRNA has beenreported to be a more sensitive marker than tyrosinase mRNA for detectedcirculating melanoma cells in peripheral blood (Tsukamoto et al., 2000,J. Dermatol. 23(2):126-131).

[0015] The ability of melanoma antigen-reactive T cells to mediate invivo tumor regression has been observed in murine tumor models and byoccasional clinical responses to adoptive immunotherapy using tumorinfiltrating lymphocytes isolated from patients with melanoma. (Kawakamiet al., 1994, Proc. Natl. Acad. Sci USA 91:6458-6462; Kawakami et al.,1995, J. Immunol. 154: 3961-3968).

[0016] In order to induce a T cell response, certain antigens must bepresented by major histocompatability complex (MHC) molecules. Molecularchaperones and heat shock proteins (“hsps”) are able to deliver boundantigens to the antigen presenting cells (“APCs”) for subsequent displayon MHC Class I or MHC Class II molecules, which in turn, may lead to thegeneration of a T cell response. (Schild et al., 1999, Current Opinionin Immunology 11:109-113). Bullock et al., 2000, J. Immunol.164(5):2354-2361 report that the density of tyrosinase and gp100peptides displayed by dendritic cells, a type of APC, affects the sizeof the CD8+ cytotoxic T cell population activated.

[0017] However, many antigens do not bind sufficiently well to heatshock proteins or other molecular chaperones for them to be efficientlydelivered to APCs. It has been discovered that attaching certainmolecules, particularly specific peptides, to an antigen can increasethe affinity of the antigen toward an hsp or other molecular chaperone.This process, termed “javelinization”, is described in InternationalPatent Application Nos. PCT/US96/13363 and PCT/US98/22335 by Rothman etal., inventors. According to the present invention, this process of“javelinization” is used to promote the association between melanomaantigens and heat shock proteins in novel methods for the treatment ofmelanoma.

3. SUMMARY OF THE INVENTION

[0018] The present invention relates to immunotherapeutic compositionscomprising an effective amount of a heat shock protein, preferablyhsp70, non-covalently bound to one or more javelinized melanoma antigensand to methods of using the immunotherapeutic compositions to induce animmune response against melanoma in a subject. The immunotherapeuticcomposition may contain one or more heat shock proteins, such as one ormore of hsp70, hsp90, gp96, BiP, hspl 70 and hsp40, and may contain oneor more javelinized melanoma antigens.

4. DETAILED DESCRIPTION OF THE INVENTION

[0019] The present invention provides a method of producing an immuneresponse in a subject against melanoma antigens. This is achieved by thegeneral step of immunizing the subject with an immunotherapeuticcomposition comprising one or more heat shock proteins non-covalentlybound to one or more javelinized melanoma antigens. The heat shockproteins are preferably mammalian heat shock proteins, and preferablyoriginate from the same species as that of the subject to be treated.

4.1.1 Melanoma Antigens

[0020] A “melanoma antigen”, as that term is used herein, is anymolecule (including a protein, lipid, or carbohydrate or a combinationor derivative thereof) which can induce a selective immune responseagainst melanoma cells. An immune response is selective against melanomacells if it is directly cytotoxic (e.g., via cytotoxic T cells ornatural killer cells) to melanoma cells or indirectly cytotoxic (e.g.,antibody directed cellular cytotoxicity) to melanoma cells but notsubstantially directly or indirectly cytotoxic to non-melanoma cells.

[0021] The immune response is considered to be substantially directly orindirectly cytotoxic to melanoma cells if the response may be clinicallycorrelated with a slowing or arrest of progression of melanoma tumorgrowth or spread.

[0022] The immune response is considered to be directly or indirectlycytotoxic to non-melanoma cells in a subject if unacceptable clinicaltoxicity is observed. The toxic side effects, and the extent of toxiceffects, of cancer chemotherapeutic agents approved by the United StatesFood and Drug Administration used in their standard doses may beconsidered to represent acceptable clinical toxicity. Acceptableclinical toxicity may occur if, for example, a melanoma antigen isexpressed at low levels in a non-melanoma cell (defined as any somaticor germ cell other than a melanoma cell, including, but not limited to,melanocytes and other pigment-containing cells) but at higher levels ina melanoma cell.

[0023] Melanoma antigens may be derived from malignant tissue or celllines or be prepared by chemical and/or recombinant methods. Themelanoma antigen may comprise one or more melanoma selective epitopesand may also comprise non-immunogenic structures. The epitope may, insome non-limiting embodiments, be characterized (e.g., its chemicalstructure and/or peptide sequence may be known). Alternatively, theepitope(s) may be uncharacterized, but presumed to be present in themolecule because that molecule induces a melanoma selective immuneresponse in an appropriate subject.

[0024] For example, the melanoma antigen of the invention may compriseelements such that it is MHC-restricted, in that its capacity to inducean immune response is restricted to a particular MHC class I or II type(see Kubo et al., 1994, J. Immun. 152:3913). Under such circumstances,the melanoma antigen may be engineered to comprise one or more naturalor heteroclitic MHC class I and/or MHC class II binding peptides, wherethe binding peptide may be distinct from the epitope(s) or the samepeptide may serve as both epitope and binding peptide. Such an antigenis desirably administered to subjects manifesting the appropriate MHCtype. The need for incorporating an MHC binding peptide may varydepending on the nature and number of epitopes comprised in the melanomaprotein antigen; Yang et al., 2000, J. Immunol. 164(8):4202-4211 reportthat genetically modified dendritic cells that express an entiremelanoma protein antigen present a wide array of possible CTL epitopesand may therefore be substantially less HLA restricted than smallerpeptide antigens. It may be desirable to select or modify antigens tobind to HLA supertypes, where a “supertype” is a group of HLA typeswhich exhibit overlapping peptide-binding repertoires (Sette and Sidney,1998, Curr. Opin. Immunol. 10:478-482). The MHC restriction of severalof the peptide antigens provided for herein is specified below.

[0025] In alternative embodiments, the melanoma antigens are notrestricted to one HLA type but are recognizable by a plurality ofHLA-types for induction of an immune response.

[0026] In one set of non-limiting embodiments of the invention, themelanoma antigen may be a ganglioside, including, but not limited to,GM2 (see Livingston, 1998, Semin. Oncol. 25(6):636-645) or GD3.

[0027] In another set of non-limiting embodiments, the melanoma antigenmay be a protein or a peptide. A “protein antigen” is a moleculecomprising more than 50 amino acid residues. A “peptide antigen” is amolecule comprising between 5 and 49 amino acid residues. The desirablesize of a melanoma antigen may vary depending upon the number andchemical nature of the above-mentioned elements comprised. For example,melanoma selective CTL epitopes according to the invention typicallycomprise between 8 and 15, and preferably between 8 and 10, amino acids,so that a melanoma antigen according to the invention which comprises aCTL epitope desirably includes at least 8 amino acids, and preferablybetween 8 and 15 amino acids. Where the melanoma antigen is a protein,it may be a naturally occurring protein or a variant thereof or may be afusion protein.

[0028] Protein antigens and peptide antigens, as those terms are usedherein, encompass molecules which have been modified or naturallycontain carbohydrate or lipid residues, non-naturally occurring aminoacids, amino acid analogs, or other covalently linked molecules, such asa benzoquinone ansamycin antibiotic or a portion thereof.

[0029] Specific non-limiting examples of such modifications includethose which improve stability of the protein or peptide. For example,but not by way of limitation, Brinckerhoffet al., 1999, Int. J. Cancer83(3:326-334 report that terminal modifications inhibit proteolyticdegradation of an immunogenic MART-1 (27-35) peptide. Miconnet et al.,2000, J. Biol. Chem. 275(35):26892-26897 report that amino acid identityor position determines the proteosomal cleavage of the MAGE-3 peptide(271-279). Other specific non-limiting examples of such modificationsinclude those which enhance the ability of a melanoma antigen to producean immune response. For example, Minev et al., 2000, Eur. J. Immunol.30(8):2115-2124 report that the addition of synthetic signal sequencesat the N-terminus of MART-1 enhanced MHC class I presentation. Ayyoub etal., 1999, J. Biol. Chem. 274:10227-10234 describes “a structure-basedapproach to designing non-natural peptides that can activateanti-melanoma cytotoxic T cells”. Guichard et al., 2000, J. Med. Chem.43(20):3803-3808 report results that suggest that substitution of aplurality of amino acids and the use of beta-amino acid substituents maybe useful modifications for increasing MHC binding capacity. It shouldbe noted, however, as stated in De Berardinis et al., 1997, HumanImmunol. 54:189-193, that altering the sequences bordering epitopes mayalter the composition of the population of T cells primed, relative tothe naturally occurring epitope.

[0030] As regards specific peptides set forth in the following sections,variants may be created by amino acid modifications or by geneticallyengineering substitutions, deletions, insertions or additions to thenaturally occurring sequence. The naturally occurring peptide or proteinmay, for example, be modified by substituting one or more amino acidswith a non-naturally occurring amino acid or an amino acid analog.Further, the naturally occurring or variant peptide or protein may beconjugated to a second molecule, such as a peptide or protein, acarbohydrate, a lipid, or a benzoquinone ansamycin antibiotic.

[0031] The present invention further provides for fragments of thespecifically recited antigens provided that they retain the melanomaspecific or selective epitope; the skilled artisan would be able toidentify the epitope-containing region using standard techniques. Inaddition, as set forth below, a melanoma antigen is modified in thesense that it is conjugated to a javelin molecule.

[0032] A melanoma antigen for use according to the invention may beidentified by any method known in the art (see, for example, Reynolds etal., 2000, J. Immunol. Methods 244:59-67 and Noppen et al., 2000, Int.J. Cancer 87(2:241-246). Non-limiting examples of suitable melanomaantigens described in the following subsections include the melanomaprotein antigens tyrosinase, tyrosinase-related proteins 1 and 2, gp100,MART, MAGE and BAGE antigens, and NY-ES01, as well as epitope-containingpeptide fragments thereof. Alternatively, the melanoma antigen may be avariant of a tyrosinase, tyrosinase related protein 1 or 2, gp100, MART,BAGE, GAGE, NY-ES01 or MAGE protein or an epitope-containing fragmentthereof.

4.1.2. Tyrosinase

[0033] Tyrosinase (EC 1.14.18.1) is a melanosomal glycoprotein that isessential in melanin synthesis. The tyrosinase gene, originally clonedat Memorial Sloan Kettering Cancer Center (MSKCC) consists of five exonsand is localized to chromosome 11q14-q21. The GeneBank Accession Numberfor the human tyrosinase sequence is XM 006020. See Bouchar et al.,1989, J. Exp. Med. 169:2029; see also Kwon et al., 1987, Proc. Natl.Acad. Sci. U.S.A. 84:7473-7477 and Ponnazhagan et al., 1994, J. Invest.Dermatol. 102:744-748. Immunophenotyping of melanomas for tyrosinase isdescribed in Chen et al., 1995, Proc. Natl. Acad. Sci. U.S.A.92:8125-8129. Any epitope of tyrosinase which falls within thedefinition of a melanoma specific antigen set forth herein may beutilized according to the invention.

[0034] Tyrosinase has been reported to be recognized by cytotoxic Tcells from melanoma patients, and peptides from the signal peptide andfrom the catalytic domain have been implicated as being particularlyrelevant (Brichard et al., 1993, J. Exp. Med. 178:489-495; Robbins etal., 1994, Cancer Res. 54:3124-3126; Wolfel et al., 1994, Eur. J.Immunol. 24:759-764).

[0035] In preferred embodiments of the invention, one or both of thefollowing previously described epitope-containing peptides (presented asthe single letter code for amino acids) may be utilized as melanomaantigens: YMNGTMSQV (SEQ ID NO: 1; Wolfel et al., 1994, Eur. J. Immunol.24:759-764) and/or MLLAVLYVL (SEQ ID NO: 2; Skipper et al.,1996, J. Exp.Med. 183(2):527-534), or epitope-containing fragments thereof. It shouldbe noted that peptides may be referred to herein in the alternative byeither the single letter or three letter code.

[0036] In another specific embodiment of the invention, a modificationof YMNGTMSQV (SEQ ID NO: 1) may be used, namely YMDGTMSQV (SEQ ID NO: 3)(or an epitope-containing fragment thereof), termed tyrosinase:368-376(370D), which corresponds to amino acids 368 to 376 of the tyrosinaseprotein modified at 370th amino acid position to substitute asparticacid for asparagine. This peptide has been tested in a clinical trialand was well tolerated with little toxicity. Two of nine vaccinatedpatients showed an increase in T cell responsiveness against tryosinaseafter immunization with the tyorinase peptide antigen by the ELISPOTassay. (Lewis et al.,2000, Int. J. Cancer 87(3):391-398).

4.1.3. Tyrosinase Related Proteins

[0037] Tyrosine related proteins, such as the differentiation antigensTRP-1 (GeneBank Accession No XM 005426) and TRP-2 (GeneBank Accession NoD17547; Yokoyama et al., 1994), S69231 (Bouchard et al., 1994), andepitope-containing peptide portions thereof, may also be used asmelanoma antigens. Specific nonlimiting examples of TRP-2 peptidescontaining melanoma specific/selective epitopes which may be usedaccording to the invention include: ORF3P (TRP-1) MSLQRQFLR (SEQ ID NO:4; Coulie et al., 1995, Proc. Natl. Acad. Sci. U.S.A. 92:7976-7980);TRP-2(180-188) SVYDFFVWL (SEQ ID NO: 5; Bowne et al., 1999, J. Exp. Med.190:1717-1722); TRP-2 (197-205) LLGPGRPYR (SEQ ID NO: 6; Wang et al.,1996, J. Exp. Med. 184:2207-2216); TRP-2(288-296), SLDDYNHLV (SEQ ID NO:7; Sun et al., 2000, Int. J. Cancer 87(3):399-404;HLA-A*0201-restricted), TRP-2(360-368) TLDSQVMSL (SEQ ID NO: 8; Noppenet al., 2000, Int. J. Cancer 87(2):241-246; HLA-A*0201-restricted) andTRP-2(476-484) VMGTLVALV (SEQ ID NO: 9; Noppen et al., 2000, Int. J.Cancer 87(2):241-246; HLA-A*0201-restricted), or modified versions orepitope-containing fragments thereof

4.1.4.GP100

[0038] Any epitope of gp100 (GeneBank Accession No. S73003) which fallswithin the definition of a melanoma specific antigen set forth hereinmay be utilized according to the invention. In nonlimiting embodimentsof the invention, gp100 is primarily recognized in the context ofHLA-A*0201.

[0039] Nonlimiting examples of suitable peptide antigens derived fromthe gp100 melanoma antigen include ITDQVPFSV (SEQ ID NO: 10), TITDQVPFSV(SEQ ID NO: 11), YLEPGVTVA (SEQ ID NO: 12), YLEPGVTVA (SEQ ID NO: 13),KTWGQYWQV (SEQ ID NO:14), TWGQYWQVL (SEQ ID NO:15), VLKRCLLHL (SEQ IDNO: 16), LNVSLADTN (SEQ ID NO: 17), SLADTNSLAV (SEQ ID NO: 18),LLDGTATLRL (SEQ ID NO: 19), VLYRYGSFSV (SEQ ID NO: 20), ALDGGNKHFL (SEQID NO: 21), and VLPSPACQLV (SEQ ID NO: 22) and epitope-containingfragments thereof (see U.S. Pat. No. 5,844,075). Regarding peptideantigens, see also Yang et al., 2000, J. Immunol. 164(8):4204-4211.

[0040] In a preferred nonlimiting embodiment of the invention, one ofthe epitope-containing peptides, ITDQVPFSV (SEQ ID NO: 10) has beenmodified at the second position, corresponding to gp100:209-217, tosubstitute methionine for threonine and yield IMDQVPFSV (SEQ ID NO: 23)to increase the affinity of binding to HLA-A0201. (Parkhurst et al.,1996, J. Immunol. 157(6):2539-2548). Immunization with this peptide hasbeen reported to induce anti-gp 100 T cell reactivity that could bedetected without extensive preliminary in vitro sensitization suggestingthat immunization with this peptide can efficiently expand thepopulation of anti-gp100 T cells.

4.1.5. MART-1/Melan A

[0041] MART-1 (Melanoma Antigen Recognized by T-Cells-1)(GeneBankAccession No. U06452 for MART, and, for Melan A, NM 005511 and XM005519)is a melanocyte differentiation antigen (U.S. Pat. No. 5,874,560 byKawakami, Brinckerhoff et al., 1999, Int. J. Cancer 83(3):326-334;Zarour et al., 2000, Proc. Natl. Acad. Sci. U.S.A. 97(1):400-405;Kawakami et al., 1994, Proc. Natl. Acad. Sci. U.S.A. 91:6458-6462;Castelli et al.,1995, J. Exp. Med. 181(1):363-368). Any epitope ofMART-1 which falls within the definition of a melanoma specific antigenset forth herein may be utilized according to the invention.

[0042] Particular peptides which include melanoma specific epitopesinclude MART-1 (51-73) and MART-1 (27-35) (AAGIGILTV; SEQ ID NO:24),which may be sources of melanoma antigens. Nonlimiting examples ofMART-1 peptide antigens derived from the MART-1 protein antigen includeILTVILGVL (SEQ ID NO: 25), EAAGIGILTV (SEQ ID NO: 26) and AAGIGILTVI(SEQ ID NO: 27) (Kawakami et al., 1994, J. Exp. Med. 180:347-352), orepitope-containing fragments thereof A further example is [Leu(28),beta-HIle(30)]MART-1 (27-35), as described in Guichard et al., 2000, J.Med. Chem. 43(20):3803-3808.

4.1.6. Mage Antigens

[0043] MAGE antigens include the products of a gene family includingMAGE-1 to −12 (now named MAGE-A1-A12, MAGE-B1 to B4, and MAGE-C1), andfour newly identified MAGE genes, namely MAGE-B5, MAGE-B6, MAGE-C2 andMAGE-C3 (Lucas et al., 2000, Int. J. Cancer 87(1):55-60), as well asgenes homologous thereto which are considered to be included in the MAGEgene family. Any epitope of a protein of the MAGE family which fallswithin the definition of melanoma specific antigen set forth herein maybe utilized according to the invention. Gibbs et al., 2000, MelanomaRes. 10(3:259-264 report that MAGE-12 and MAGE-6 are expressed bymelanoma cells at higher frequencies than other MAGE genes, andtherefore may be particularly useful. The GeneBank Accession Numbersare, for MAGE A1: NM 004988; MAGE A2: NM 005361; MAGE A3: NM 020017;MAGE A4: NM 002362; MAGE A6: NM 005363; MAGE A12: NM 005367.

[0044] Non-limiting examples of peptide antigens derived from MAGE-1protein antigen include ALEAQQEAL (SEQ ID NO: 28), ILESLFRAV (SEQ ID NO:29), SLHCKPEEAL (SEQ ID NO: 30), PLVLGTLEEV (SEQ ID NO: 31) andepitope-containing fragments thereof. Non-limiting examples of peptideantigens derived from MAGE-1/3 include CLGLSYDGL (SEQ ID NO: 32),LLKYRAREPV (SEQ ID NO: 33) and epitope-containing fragments thereof; andnonlimiting examples of peptide antigens derived from MAGE-3 includeMAGE-3(271-279), particularly FLWGPRALV (SEQ ID NO:34) andepitope-containing fragments thereof. (Miconnet et al., 2000, J. Biol.Chem. 275:26892-26897; International Patent Application No.PCT/US94/02353 by Cytel, Van der Bruggen et al. inventors). Anotherexample of a peptide antigen that may be used according to the inventionis the MAGE-A1 peptide EADPTGHSY (SEQ ID NO: 35), which is HLA-A1 andHLA-B35 restricted (Luiten et al., 2000, Tissue Antigens 56(1):77-81).

4.1.7. Javelinization of Antigens

[0045] Heat shock protein 70 (“hsp70”) has been shown to be effective atdelivering bound peptide antigens to antigen presenting cells for theirdisplay on MHC class I molecules. Immunization of mice with hsp70-boundantigens has resulted in the generation of strong cellular immuneresponses against the chosen antigen. However, in vitro experimentationhas shown that many optimal MHC class I binding antigens do not bindwell to hsp70. Binding of diverse antigens to various heat shockproteins can be facilitated by “javelinization” (Moroi et al., 2000,Proc Natl. Acad. Sci. U.S.A. 97(7):3485-3490).

[0046] The term “javelin” as used herein refers to a molecule whichitself is capable of non-covalently binding to a heat shock protein, andwhich, when covalently linked to a melanoma antigen, acts as a tether,creating a non-covalent physical association between the melanomaantigen and the heat shock protein.

[0047] The javelin may be a member of any class of biochemical moleculeor combination thereof, but is preferably a peptide or a peptidomimeticcompound. The particular structure of a javelin will depend, to at leastsome degree, on the heat shock protein to which it binds. It should benoted, however, that because particular heat shock proteins act asmolecular chaperones in the process of protein folding, they aretypically capable of binding to a variety of javelin molecules. Suitablejavelin molecules, and methods for identifying further javelinmolecules, are described in co-pending International Patent ApplicationNo. PCT/US98/22335, incorporated by reference in its entirety herein.

[0048] Accordingly, the javelin to be covalently linked to a melanomaantigen is chosen based on the particular heat shock protein or heatshock proteins to which it is intended to bind. Such heat shock proteinmay be any known or yet to be identified heat shock protein or portionthereof, or any fusion protein comprising at least a portion of a heatshock protein. The term “heat shock protein”, as used herein, refers tostress proteins (including homologs thereof expressed constitutively),including, but not limited to, gp96, hsp170, hsp90, BiP, hsp70, hsp60,hsp40, hsc70, and hsp10. Hsp target may be prepared from a naturalsource, expressed recombinantly, or chemically synthesized.

[0049] In particular, non-limiting embodiments of the invention,javelins may have amino acid compositions which comprise a substantialproportion of hydrophobic amino acids such as phenylalanine andtryptophan, and to a lesser extent, leucine and/or a substantial numberof serine, threonine, or proline residues. In particular, nonlimitingembodiments, javelins of the invention may comprise amino acid sequenceswhich have the general descriptionhydrophobic—basic—hydrophobic—hydrophobic—hydrophobic;Ser/Thr—hydrophobic—hydrophobic—Ser/Thr;Ser/Thr—Ser/Thr—hydrophobic—hydrophobic—Ser/Thr—Ser/Thr; andSer/Thr—Ser/Thr—Hydrophobic—hydrophobic—hydrophobic. Alternatively,javelins may comprise heat shock binding peptides as described inBlond-Elguindi et al., 1993, Cell 75:717-728, including the consensussequencehydrophobic—(Trp/Xaa)—hydrophobic—Xaa—hydrophobic—Xaa—hydrophobic (whereXaa may be any amino acid) and the specific peptides His Trp Asp Phe AlaTrp Pro Trp (SEQ ID NO: 36) and Phe Trp Gly Leu Trp Pro Trp Glu (SEQ IDNO: 37); Auger et al., 1996, Nature Med. 2:306-310, including Gin LysArg Ala Ala (SEQ ID NO:38) and Arg Arg Arg Ala Ala (SEQ ID NO:39); Flynnet al., 1989, Science 245:385-390; Gragerov et al., 1994, J. Mol. Biol.235:848-854; Terlecky et al., 1992, J. Biol. Chem. 267:9202-9202, LysPhe Glu Arg Gin (SEQ ID NO: 40); and Nieland et al., 1996, Proc. Natl.Acad. Sci. U.S.A. 93:6135-6139, including the VSV8 peptide, Arg Gly TyrVal Tyr Gin Gly Leu (SEQ ID NO: 41). In preferred embodiments, javelinsof the invention may have a length of 4-50 amino acid residues, and morepreferably 7-20 amino acid residues.

[0050] In specific, non-limiting embodiments, the following amino acidsequences, discussed more fully in International Patent Application No.PCT/US98/22335, may be covalently linked to melanoma antigens accordingto the invention: Tyr Thr Leu Val Gln Pro Leu; (SEQ ID NO: 42) Thr ProAsp Ile Thr Pro Lys; (SEQ ID NO: 43) Thr Tyr Pro Asp Leu Arg Tyr; (SEQID NO: 44) Asp Arg Tbr His Ala Thr Ser; (SEQ ID NO: 45) Met Ser Tbr ThrPhe Tyr Ser; (SEQ ID NO: 46) Tyr Gln His Ala Val Gln Thr; (SEQ ID NO:47) Phe Pro Phe Ser Ala Ser Thr; (SEQ ID NO: 48) Ser Ser Phe Pro Pro LeuAsp; (SEQ ID NO: 49) Met Ala Pro Ser Pro Pro His; (SEQ ID NO: 50) SerSer Phe Pro Asp Leu Leu; (SEQ ID NO: 51) His Ser Tyr Asn Arg Leu Pro;(SEQ ID NO: 52) His Leu Tbr His Ser Gln Arg; (SEQ ID NO: 53) Gln Ala AlaGln Ser Arg Ser; (SEQ ID NO: 54) Phe Ala Thr His His Ile Gly; (SEQ IDNO: 55) Ser Met Pro Glu Pro Leu Ile; (SEQ ID NO: 56) Ile Pro Arg Tyr HisLeu Ile; (SEQ ID NO: 57) Ser Ala Pro His Met Thr Ser; (SEQ ID NO: 58)Lys Ala Pro Val Trp Ala Ser; (SEQ ID NO: 59) Leu Pro His Trp Leu LeuIle; (SEQ ID NO: 60) Ala Ser Ala Gly Tyr Gln Ile; (SEQ ID NO: 61) ValThr Pro Lys Tbr Gly Ser; (SEQ ID NO: 62) Glu His Pro Met Pro Val Leu;(SEQ ID NO: 63) Val Ser Ser Phe Val Thr Ser; (SEQ ID NO: 64) Ser Thr HisPhe Thr Trp Pro; (SEQ ID NO: 65) Gly Gln Trp Trp Ser Pro Asp; (SEQ IDNO: 66) Gly Pro Pro His Gln Asp Ser; (SEQ ID NO: 67) Asn Thr Leu Pro SerThr Ile; (SEQ ID NO: 68) His Gln Pro Ser Arg Trp Val; (SEQ ID NO: 69)Tyr Gly Asn Pro Leu Gln Pro; (SEQ ID NO: 70) Phe His Trp Trp Trp GlnPro; (SEQ ID NO: 71) Ile Thr Leu Lys Tyr Pro Leu; (SEQ ID NO: 72) PheHis Trp Pro Trp Leu Phe; (SEQ ID NO: 73) Thr Ala Gln Asp Ser Thr Gly;(SEQ ID NO: 74) Phe His Trp Trp Trp Gln Pro; (SEQ ID NO: 75) Phe His TrpTrp Asp Trp Trp; (SEQ ID NO: 76) Glu Pro Phe Phe Arg Met Gln; (SEQ IDNO: 77) Thr Trp Trp Leu Asn Tyr Arg; (SEQ ID NO: 78) Phe His Trp Trp TrpGln Pro; (SEQ ID NO: 79) Gln Pro Ser His Leu Arg Trp; (SEQ ID NO: 80)Ser Pro Ala Ser Pro Val Tyr; (SEQ ID NO: 81) Phe His Trp Trp Trp GlnPro; (SEQ ID NO: 82) His Pro Ser Asn Gln Ala Ser; (SEQ ID NO: 83) AsnSer Ala Pro Arg Pro Val; (SEQ ID NO: 84) Gln Leu Trp Ser Ile Tyr Pro;(SEQ ID NO: 85) Ser Trp Pro Phe Phe Asp Leu; (SEQ ID NO: 86) Asp Thr ThrLeu Pro Leu His; (SEQ ID NO: 87) Trp His Trp Gln Met Leu Trp; (SEQ IDNO: 88) Asp Ser Phe Arg Thr Pro Val; (SEQ ID NO: 89) Thr Ser Pro Leu SerLeu Leu; (SEQ ID NO: 90) Ala Tyr Asn Tyr Val Ser Asp; (SEQ ID NO: 91)Arg Pro Leu His Asp Pro Met; (SEQ ID NO: 92) Tip Pro Ser Thr Thr LeuPhe; (SEQ ID NO: 93) Ala Thr Leu Glu Pro Val Arg; (SEQ ID NO: 94) SerMet Thr Val Leu Arg Pro; (SEQ ID NO: 95) Gln Ile Gly Ala Pro Ser Trp;(SEQ ID NO: 96) Ala Pro Asp Leu Tyr Val Pro; (SEQ ID NO: 97) Arg Met ProPro Leu Leu Pro; (SEQ ID NO: 98) Ala Lys Ala Thr Pro Glu His; (SEQ IDNO: 99) Thr Pro Pro Leu Arg Ile Asn; (SEQ ID NO: 100) Leu Pro Ile HisAla Pro His; (SEQ ID NO: 101) Asp Leu Asn Ala Tyr Thr His; (SEQ ID NO:102) Val Thr Leu Pro Asn Phe His; (SEQ ID NO: 103) Asn Ser Arg Leu ProThr Leu; (SEQ ID NO: 104) Tyr Pro His Pro Ser Arg Ser; (SEQ ID NO: 105)Gly Thr Ala His Phe Met Tyr; (SEQ ID NO: 106) Tyr Ser Leu Leu Pro ThrArg; (SEQ ID NO: 107) Leu Pro Arg Arg Thr Leu Leu; (SEQ ID NO: 108) ThrSer Thr Leu Leu Trp Lys; (SEQ ID NO: 109) Thr Ser Asp Met Lys Pro His;(SEQ lD NO: 110) Thr Ser Ser Tyr Leu Ala Leu; (SEQ ID NO: 111) Asn LeuTyr Gly Pro His Asp; (SEQ ID NO: 112) Leu Glu Thr Tyr Thr Ala Ser; (SEQID NO: 113) Ala Tyr Lys Ser Leu Thr Gln; (SEQ ID NO: 114) Ser Thr SerVal Tyr Ser Ser; (SEQ ID NO: 115) Glu Gly Pro Leu Arg Ser Pro; (SEQ IDNO: 116) Thr Thr Tyr His Ala Leu Gly; (SEQ ID NO: 117) Val Ser Ile GlyHis Pro Ser; (SEQ ID NO: 118) Thr His Ser His Arg Pro Ser; (SEQ ID NO:119) Ile Thr Asn Pro Leu Thr Thr; (SEQ ID NO: 120) Ser Ile Gln Ala HisHis Ser; (SEQ ID NO: 121) Leu Asn Trp Pro Arg Val Leu; (SEQ ID NO: 122)Tyr Tyr Tyr Ala Pro Pro Pro; (SEQ ID NO: 123) Ser Leu Trp Thr Arg LeuPro; (SEQ ID NO: 124) Asn Val Tyr His Ser Ser Leu; (SEQ ID NO: 125) AsnSer Pro His Pro Pro Thr; (SEQ ID NO: 126) Val Pro Ala Lys Pro Arg His;(SEQ ID NO: 127) His Asn Leu His Pro Asn Arg; (SEQ ID NO: 128) Tyr ThrThr His Arg Trp Leu; (SEQ ID NO: 129) Ala Val Thr Ala Ala Ile Val; (SEQID NO: 130) Thr Leu Met His Asp Arg Val; (SEQ ID NO: 131) Thr Pro LeuLys Val Pro Tyr; (SEQ ID NO: 132) Phe Thr Asn Gln Gln Tyr His; (SEQ IDNO: 133) Ser His Val Pro Ser Met Ala; (SEQ ID NO: 134) His Thr Tbr ValTyr Gly Ala; (SEQ ID NO: 135) Thr GIu Thr Pro Tyr Pro Thr; (SEQ ID NO:136) Leu Thr Tbr Pro Phe Ser Ser; (SEQ ID NO: 137) Gly Val Pro Leu ThrMet Asp; (SEQ ID NO: 138) Lys Leu Pro Thr Val Leu Arg; (SEQ ID NO: 139)Cys Arg Phe His Gly Asn Arg; (SEQ ID NO: 140) Tyr Thr Arg Asp Phe GluAla; (SEQ ID NO: 141) Ser Ser Ala Ala Gly Pro Arg; (SEQ ID NO: 142) SerLeu Ile Gln Tyr Ser Arg; (SEQ ID NO: 143) Asp Ala Leu Met Trp Pro Xaa;(SEQ ID NO: 144) Ser Ser Xaa Ser Leu Tyr Ile; (SEQ ID NO: 145) Phe AsnThr Ser Thr Arg Thr; (SEQ ID NO: 146) Tbr Val Gln His Val Ala Phe; (SEQID NO: 147) Asp Tyr Ser Phe Pro Pro Leu; (SEQ ID NO: 148) Val Gly SerMet Glu Ser Leu; (SEQ ID NO: 149) Phe Xaa Pro Met Ile Xaa Ser; (SEQ IDNO: 150) Ala Pro Pro Arg Val Thr Met; (SEQ ID NO: 151) Tie Ala Thr LysTbr Pro Lys; (SEQ ID NO: 152) Lys Pro Pro Leu Phe Gln Ile; (SEQ ID NO:153) Tyr His Thr Ala His Asn Met; (SEQ ID NO: 154) Ser Tyr Ile Gln AlaThr His; (SEQ ID NO: 155) Ser Ser Phe Ala Thr Phe Leu; (SEQ ID NO: 156)Thi Thr Pro Pro Asn Phe Ala; (SEQ ID NO: 157) Ile Ser Leu Asp Pro ArgMet; (SEQ ID NO: 158) Ser Leu Pro Leu Phe Gly Ala; (SEQ ID NO: 159) AsnLeu Leu Lys Thr Thr Leu; (SEQ ID NO: 160) Asp Gln Asn Leu Pro Arg Arg;(SEQ ID NO: 161) Ser His Phe Glu Gln Leu Leu; (SEQ ID NO: 162) Tbr ProGln Leu His His Gly; (SEQ ID NO: 163) Ala Pro Leu Asp Arg Ile Thr; (SEQID NO: 164) Phe Ala Pro Leu Ile Ala His; (SEQ ID NO: 165) Ser Trp IleGln Thr Phe Met; (SEQ ID NO: 166) Asn Thr Trp Pro His Met Tyr; (SEQ IDNO: 167) Glu Pro Leu Pro Thr Thr Leu; (SEQ ID NO: 168) His Gly Pro HisLeu Phe Asn; (SEQ ID NO: 169) Tyr Leu Asn Ser Tbr Leu Ala; (SEQ ID NO:170) His Leu His Ser Pro Ser Gly; (SEQ ID NO: 171) Tbr Leu Pro His ArgLeu Asn; (SEQ ID NO: 172) Ser Ser Pro Arg Glu Val His; (SEQ ID NO: 173)Asn Gln Vat Asp Thr Ala Arg; (SEQ ID NO: 174) Tyr Pro Thr Pro Leu LeuThr; (SEQ ID NO: 175) His Pro Ala Ala Phe Pro Trp; (SEQ ID NO: 176) LeuLeu Pro His Ser Ser Ala; (SEQ ID NO: 177) Leu Glu Thr Tyr Thr Ala Ser;(SEQ ID NO: 178) Lys Tyr Val Pro Leu Pro Pro; (SEQ ID NO: 179) Ala ProLeu Ala Leu His Ala; (SEQ ID NO: 180) Tyr Glu Ser Leu Leu Thr Lys; (SEQID NO: 181) Ser His Ala Ala Ser Gly Thr; (SEQ ID NO: 182) Gly Leu AlaThr Val Lys Ser; (SEQ ID NO: 183) Gly Ala Thr Ser Phe Gly Leu; (SEQ IDNO: 184) Lys Pro Pro Gly Pro Val Ser; (SEQ ID NO: 185) Thr Leu Tyr ValSer Gly Asn; (SEQ ID NO: 186) His Ala Pro Phe Lys Ser Gln; (SEQ ID NO:187) Val Ala Phe Thr Arg Leu Pro; (SEQ ID NO: 188) Leu Pro Tbr Arg ThrPro Ala; (SEQ ID NO: 189) Ala Ser Phe Asp Leu Leu Ile; (SEQ ID NO: 190)Arg Met Asn Thr GIu Pro Pro; (SEQ ID NO: 191) Lys Met Thr Pro Leu ThrThr; (SEQ ID NO: 192) Ala Asn Ala Thr Pro Leu Leu; (SEQ ID NO: 193) TbrIle Trp Pro Pro Pro Val; (SEQ ID NO: 194) Gln Thr Lys Val Met Thr Thr;(SEQ ID NO: 195) Asn His Ala Val Phe Ala Ser; (SEQ ID NO: 196) Leu HisAla Ala Xaa Thr Ser; (SEQ ID NO: 197) Thr Trp Gln Pro Tyr Phe His; (SEQID NO: 198) Ala Pro Leu Ala Leu His Ala; (SEQ ID NO: 199) Thr Ala HisAsp Leu Thr Val; (SEQ ID NO: 200) Asn Met Thr Asn Met Leu Thr; (SEQ IDNO: 201) Gly Ser Gly Leu Ser Gln Asp; (SEQ ID NO: 202) Thr Pro Ile LysTbr Ile Tyr; (SEQ ID NO: 203) Ser His Leu Tyr Arg Ser Ser; and (SEQ IDNO: 204) His Gly Gln Ala Trp Gln Phe. (SEQ ID NO: 205)

[0051] Xaa May be any amino acid.

[0052] For covalently linking the javelin to a melanoma antigen, it maybe desirable to add, to the javelin, a “linker region” containingchemical structures which facilitate the linkage reaction. For example,where the javelin is a peptide, a linker region, preferably, but not byway of limitation, containing 1-4 amino acids may be added. As onespecific, non-limiting example, where the linking reaction utilizessulfhydrl groups, a single Cys residue, or a linker peptide such as CysGly Ser Gly (SEQ ID NO: 206) may be added to the amino- orcarboxy-terminus of a javelin peptide.

[0053] A single melanoma antigen may be attached to one or more javelinmolecules. A single javelin molecule may be attached to one or moremelanoma antigens. A javelin can be attached or incorporated anywhere inan antigen, but preferably does not substantially structurally distortthe melanoma specific/selective epitope. For example, in the case ofpeptidic antigens and one or more peptidic javelin, a javelin can bepositioned at the amino terminus of the antigen, at the carboxylterminus of the antigen, at any point within the amino acid sequence ofthe antigen, or at any combination of the above.

[0054] As specific nonlimiting examples, some of the javelinizedmelanoma antigens that can be prepared from the tyrosinase-derivedmelanoma antigen YMDGTMSQV (SEQ ID NO: 207) include the followingJav-peptides: HWDFAWPWYMDGTMSQV (SEQ ID NO: 208, YMDGTMSQVHWDFAWPW (SEQID NO: 209), HWDFAWPWYMDGTMSQVHWDFAWPW (SEQ ID NO: 210) orHWDFAWPWYMDGTMSQVWPWAFDWH (SEQ ID NO: 211), where bold face, underlinedsequence denotes the javelin and non-bold face, non-underlined sequencedenotes the antigenic sequence. Specific nonlimiting examples ofjavelinized melanoma antigens having the linker, denoted by italics, GSGinclude: HWDFAWPWGSGYMDGTMSQV (SEQ ID NO: 211) andHWDFAWPWGSGYMDGTMSQVGSGWPWAFDWH (SEQ ID NO:212).

[0055] Additional nonlimiting examples ofjavelinized melanoma antigensare provided in Tables 1-7 below. In each of the tables, xxx is an aminoacid linker between 0 and 10 amino acids long, the bold lettersrepresent the amino acid sequence of the javelin and the non-boldcapital letters represent the amino acid sequence of the melanomaantigen. In particular, Table 1 shows nonlimiting examples ofjavelinizedmelanoma antigens derived from tyrosinase (consecutively, SEQ IDNOS:213-242); Tables 2 and 3 show nonlimiting examples ofjavelinizedmelanoma antigens derived from gp100 (consecutively, SEQ IDNOS:243-382); Table 4 shows nonlimiting examples of javelinized melanomaantigens derived from MART-1 (consecutively, SEQ ID NOS: 383-422); Table5 shows nonlimiting examples of javelinized melanoma antigens derivedfrom MAGE-1 (consecutively, SEQ ID NOS: 423-462); Table 6 showsnonlimiting examples ofjavelinized melanoma antigens derived fromMAGE-1/3 (consecutively, SEQ ID NOS: 463-492); and Table 7 showsnonlimiting examples of javelinized melanoma antigens derived fromMAGE-3 (consecutively, SEQ ID NOS: 493-502). TABLE 1 Javelinizedmelanoma antigens derived from tyrosinase I. Derived from peptideYMDGTMSQV HWDFAWPWxxxYMDGTMSQV YMDGTMSQVgsgHWDFAWPWHWDFAWPWxxxYMDGTMSQVxxxHWDFAWPW HWDFAWPWYMDGTMSQV YMDGTMSQVHWDFAWPWHWDFAWPWYMDGTMSQVHWDFAWPW YMDGTMSQVxxxWPWAFDWHHWDFAWPWxxxYMDGTMSQVxxxWPWAFDWH YMDGTMSQVWPWAFDWHHWDFAWPWYMDGThISQVWPWAFDWH II. Derived from peptide YMNGTMSQVHWDFAWPWxxxYMNGTMSQV YMNGTMSQVxxxHWDFAWPWHWDFAWPWxxxYMNGTMSQVxxxHWDFAWPW HWDFAWPWYMNGTMSQV YMNGTMSQVHWDFAWPWHWDFAWPWYMNGTMSQVHWDFAWPW YMNGTMSQVxxxWPWAFDWHHWDFAWPWxxxYMNGTMSQVxxxWPWAFDWH YMNGTMSQVWPWAFDWHHWDFAWPWYMNGTMSQVWPWAFDWH III. Derived from peptide MLLAVLYCLHWDFAWPWxxxMLLAVLYCL MLLAVLYCLxxxHWDFAWPWHWDFAWPWxxxMLLAVLYCLxxxHWDFAWPW HWDFAWPWMLLAVLYCL MLLAVLYCLHWDFAWPWHWDFAWPWMLLAVLYGLHWDFAWPW MLLAVLYCLxxxWPWAFDWHHWDFAWPWxxxMLLAVLYCLxxxWPWAFDWH MLLAVLYCLWPWAFDWHHWDFAWPWMLLAVLYCLWPWAFDWH

[0056] TABLE 2 Javelinized melanoma antigens derived from Gp100(209-217) I. Derived from peiflide IMDQVPFSV HWDFAWPWxxxLMDQVPFSVIMDQVPFSVxxxHWDFAWPW** where amino acid linker xxx is gsgHWDFAWPWxxxIMDQVPFSVxxxHWDFAWPW HWDFAWPWIMDQVPFSV IMDQVPFSVHWDFAWPWHWDFAWPWIMDQVPFSVHWDFAWPW IMDQVPFSVxxxWPWAFDWHHWDFAWPWxxxIMDQVPFSVxxxWPWAFDWH IMDQVPFSVWPWAFDWHHWDFAWPWIMDQVPFSVWPWAFDWH II. Derived from peitide ITDQVPFSVHWDFAWPWxxxITDQVPFSV ITDQVPFSVxxxHWDFAWPWHWDFAWPWxxxITDQVPFSVxxxHWDFAWPW HWDFAWPWITDQVPFSV ITDQVPFSVHWDFAWPWHWDFAWPWITDQVPFSVHWDFAWPW ITDQVPFSVxxxWPWAFDWHHWDFAWPWxxxITDQVPFSVxxxWPWAFDWH ITDQVPFSVWPWAFDWHHWDFAWPWITDQVPFSVWPWAFDWH III. Derived from peptide TITDQVPFSVHWDFAWPWxxxITDQVPFSV TITDQVPFSVxxxHWDFAWPWHWDFAWPWxxxTITDQVPFSVxxxHWDFAWPW HWDFAWPWTITDQVPFSV TITDQVPFSVHWDFAWPWHWDFAWPWTITDQVPFSVHWDFAWPW TITDQVPFSVxxxWPWAFDWHHWDFAWPWxXXTITDQVPFSVxxxWPWAFDWH TITDQVPFSVWPWAFDWHHWDFAWPWTITDQVPFSVWPWAFDWH

[0057] TABLE 3 Javelinized melanoma antigens derived from Gp100(280-288) I. Derived from peptide YLEPGVTV HWDFAWPWxxxYLEPGVTVYLEPGVTVxxxHWDFAWPW HWDFAWPWxxxYLEPGVTVxxxHWDFAWPW HWDFAWPWYLEPGVTVYLEPGVTVHWDFAWPW HWDFAWPWYLEPGVTVHWDFAWPW YLEPGVTVxxxWPWAFDWHHWDFAWPWxxxYLEPGVTVxxxWPWAFDWH YLEPGVTVWPWAFDWH HWDFAWPWYLEPGVTVWPWAFDWHII. Derived from peptide YLEPGVTVA HWDFAWPWxxxYLEPGVTVAYLEPGVTVAxxxHWDFAWPW HWDFAWPWYLEPGVTVAxxxHWDFAWPW HWDFAWPWYLEPGVTVAYLEPGWfVAHWDFAWPW HWDFAWPWYLEPGVTVAHWDFAWPW YLEPGVTVAxxxWPWAFDWHHWDFAWPWxxxYLEPGVTVAxxxWPWAFDWH YLEPGVTVAWPWAFDWHHWDFAWPWYLEPGVTVAWPWAFDWH III. Derived from peptide KTWGQYWQVHWDFAWPWxxxKTWGQYWQV KTWGQYWQVxxxHWDFAWPWHWDFAWPWxxxKTWGQYWQVxxxHWDFAWPW HWDFAWPWKTWGQYWQV KTWGQYWQVHWDFAWPWHWDFAWPWKTWGQYWQVHWDFAWPW KTWGQYWQVxxxWPWAFDWHHWDFAWPWxxxKTWGQYWQVxxxWPWAFDWH KTWGQYWQVWPWAFDWHHWDFAWPWKTWGQYWQVWPWAFDWH IV. Derived from peptide KTWGQYWQVLHWDFAWPWxxxKTWGQYWQVL KTWGQYWQVLxxxHWDFAWPWHWDFAWPWxxxKTWGQYWQVLxxxHWDFAWPW HWDFAWPWKTWGQYWQVL KTWGQYWQVLHWDFAWPWHWDFAWPWKTWGQYWQVLHWDFAWPW KTWGQYWQVLxxxWPWAFDWHHWDFAWPWxxxKTWGQYWQVLxxxWPWAFDWH KTWGQYWQVLWPWAFDWHHWDFAWPWKTWGQYWQVLWPWAFDWH V. Derived from peptide VLKRCLLHLHWDFAWPWxxxVLKRCLLHL VLKRCLLHLxxxHWDFAWPWHWDFAWPWxxxVLKRCLLHLxxxHWDFAWPW HWDFAWPWVLKRCLLHL VLKRCLLHLHWDFAWPWHWDFAWPWVLKRCLLHLHWDFAWPW VLKRCLLHLxxxWPWAFDWHHWDFAWPWxxxVLKRCLLHLxxxWPWAFDWH VLKRCLLHLWPWAFDWHHWDFAWPWVLKRCLLHLWPWAFDWH VI. Derived from petide LNVSLADTNHWDFAWPWxxxLNVSLADTN LNVSLADTNxxxHWDFAWPWHWDFAWPWxxxLNVSLADTNxxxHWDFAWPW HWDFAWPWLNVSLADTN LNVSLADTNHWDFAWPWHWDFAWPWLNVSLADTNHWDFAWPW LNVSLADTNxxxWPWAFDWHHWDFAWPWxxxLNVSLADTNxxxWPWAFDWH LNVSLADTNWPWAFDWHHWDFAWPWLNVSLADTNWPWAFDWH VII. Derived from peptide SLADTNSLAVHWDFAWPWxxxSLADTNSLAV SLADTNSLAVxxxHWDFAWPWHWDFAWPWxxxSLADTNSLAVxxxHWDFAWPW HWDFAWPWSLADTNSLAV SLADTNSLAVHWDFAWPWHWDFAWPWSLADTNSLAVxxxHWDFAWPW SLADTNSLAVxxxWPWAFDWHHWDFAWPWxxxSLADTNSLAVxxxWPWAFDWH SLADTNSLAVWPWAFDWHHWDFAWPWSLADTNSLAVWPWAFDWH VIII. Derived from peptide LLDGTATLRLHWDFAWPWxxxLLDGTATLRL LLDGTATLRLXXXHWDFAWPWHWDFAWPWxxxLLDGTATLRLxxxHWDFAWPW HWDFAWPWLLDGTATLRL LLDGTATLRLHWDFAWPWHWDFAWPWLLDGTATLRLHWDFAWPW LLDGTATLRLxxxWPWAFDWHHWDFAWPWxxxLLDGTATLRLxxxWPWAFDWH LLDGTATLRLWPWAFDWHHWDFAWPWLLDGTATLRLWPWAFDWH IX. Derived from peptide VLYRYGSFSVHWDFAWPWxxxVLYRYGSFSV VLYRYGSFSVxxxHWDFAWPWHWDFAWPWxxxVLYRYGSFSVxxxHWDFAWPW HWDFAWPWVLYRYGSFSV VLYRYGSFSVHWDFAWPWHWDFAWPWVLYRYGSFSVHWDFAWPW VLYRYGSFSVxxxWPWAFDWHHWDFAWPWxxxVLYRYGSFSVxxxWPWAFDWH VLYRYGSFSVWPWAFDWHHWDFAWPWVLYRYGSFSVWPWAFDWH X. Derived from peptide ALDGGNKHFLHWDFAWPWxxxALDGGNKHFL ALDGGNKHFLxxxHWDFAWPWHWDFAWPWxxxALDGGNKHFLxxxHWDFAWpW HWDFAWPWALDGGNKHFL ALDGGNKHFLHWDFAWPWHWDFAWPWALDGGNKHFLHWDFAWPW ALDGGNKHFLxxxWPWAFDWHHWDFAWFWxxxALDGGNKHFLxxxWPWAFDWH ALDGGNKHFLWPWAFDWHHWDFAWPWALDGGNKHFLWPWAFDWH XI. Derived from peptide VLPSPACOLVHWDFAWPWxxxVLPSPACQLV VLPSPACQLVxxxHWDFAWPWHWDFAWPWxxxVLPSPACQLVxxxHWDFAWPW HWDFAWPWVLPSPACQLV VLPSPACQLVHWDFAWPWHWDFAWPWVLPSPACQLVHWDFAWPW VLPSPACQLVxxxWPWAFDWHHWDFAWPWxxxVLPSPACQLVxxxWPWAFDWH VLPSPACQLVWPWAFDWHHWDFAWPWVLPSPACQLVWPWAFDWH

[0058] TABLE 4 Javelinized melanoma antigens derived from MART-1/MELAN AI. Derived from peptide AAGIGILTV HWDFAWPWxxxAAGIGILTVAAGIGILTVxxxHWDFAWPW HWDFAWPWxxxAAGIGILTVxxxHWDFAWPW HWDFAWPWAAGIGILTVAAGIGILTVHWDFAWPW HWDFAWPWAAGIGILTVHWDFAWPW AAGIGILTVmWPWAFDWHHWDFAWPWxxxAAGIGILTVxxxWPWAFDWH AAGIGILTVWPWAFDWHHWDFAWPWAAGIGILTVWPWAFDWH II. Derived from peptide EAAGIGILTVHWDFAWPWxxxEAAGIGLLTV EAAGIGILTVxxxHWDFAWPWHWDFAWPWxxxEAAGIGILTVxxxHWDFAWPW HWDFAWPWEAAGIGILTV EAAGIGILTVHWDFAWPWHWDFAWPWEAAGIGILTVHWDFAWPW EAAGIGILTVxxxWPWAFDWHHWDFAWPWxxxEAAGIGILTVxxxWPWAFDWH EAAGIGILTVWPWAFDWHHWDFAWPWEAAGIGILTVWPWAFDWH III. Derived from peptide EAAGOGILTVIHWDFAWPWxxxEAAGQGILTVI EAAGOGILTVIxxxHWDFAWPWHWDFAWPWxxxEAAGOGILTVIxxxHWDFAWPW HWDFAWPWEAAGOGILTVIEAAGOGILTVIHWDFAWPW HWDFAWPWEAAGOGILTVIHWDFAWPW EAAGOGILTVIxxxWPWAFDWHHWDFAWPWxxxEAAGOGILTVIxxxWPWAFDWH EAAGOGILTVIWPWAFDWHHWDFAWPWEAAGOGILTVIWPWAFDWH IV. Derived from peptide ILTVILGVLHWDFAWPWxxxILTVILGVL ILTVILGVLxxxHWDFAWPWHWDFAWPWxxxILTVILGVLxxxHWDFAWPW HWDFAWPWILTVILGVL ILTVILGVLHWDFAWPWHWDFAWPWILTVILGVLHWDFAWPW ILTVILGVLxxxWPWAFDWHHWDFAWPWxxxILTVILGVLxxxWPWAFDWH ILTVILGVLWPWAFDWHHWDFAWPWILTVILGVLWPWAFDWH

[0059] TABLE 5 Javelinized melanoma antigens derived from MAGE-1 I.Derived from MAGE-1(15) (peptide ALEAQQEAL) HWDFAWPWxxxALEAQQEALALEAQQEALxxxHWDFAWPW HWDFAWPWxxxALEAQQEALxxxHWDFAWPW HWDFAWPWALEAQQEALALEAQQEALHWDFAWPW HWDFAWPWALEAQQEALHWDFAWPW ALEAQQEALxxxWPWAFDWHHWDFAWPWxxxALEAQQEALxxxWPWAFDWH ALEAQQEALWPWAFDWHHWDFAWPWALEAQQEALWPWAFDWH II. Derived from MAGE-1 (93) (peptideILESLFRAV) HWDFAWPWxxxILESLFRAV ILESLFRAVxxxHWDFAWPWHWDFAWPWxxxILESLFRAVxxxHWDFAWPW HWDFAWPWILESLFRAV ILESLFRAVHWDFAWPWHWDFAWPWILESLFRAVHWDFAWPW ILESLFRAVxxxWPWAFDWHHWDFAWPWxxxILESLFRAVxxxWPWAFDWH ILESLFRAVWPWAFDWHHWDFAWPWILESLFRAVWPWAFDWH III. Derived from MAGE-1 (7) (peptideSLHCKPEEAL) HWDFAWPWxxxSLHCKPEEAL SLHCKPEEALxxxHWDFAWPWHWDFAWPWxxxSLHCKPEEALxxxHWDFAWPW HWDFAWPWSLHCKPEEAL SLHCKPEEALHWDFAWPWHWDFAWPWSLHCKPEEALHWDFAWPW SLHCKPEEALxxxWPWAFDWHHWDFAWPWxxxSLIIGKPEEALxxxWPWAFDWH SLHCKPEEALWPWAFDWHHWDFAWPWSLHCKPEEALWPWAFDWH IV. Derived from MAGE-1 (37) peptidePLVLGTLEEV) HWDFAWPWxxxPLVLGTLEEV PLVLGTLEEVxxxHWDFAWPWHWDFAWPWxxxPLVLGTLEEVxxxHWDFAWPW HWDFAWPWPLVLGTLEEV PLVLGTLEEVHWDFAWPWHWDFAWPWPLVLGTLEEVHWDFAWPW PLVLGTLEEVxxxWPWAFDWHHWDFAWPWxxxPLVLGTLEEVxxxWPWAFDWH PLVLGTLEEVWPWAFDWHHWDFAWPWIPLVLGTLEEVWPWAFDWH

[0060] TABLE 6 Javelinized melan ma antigens derived from MAGE 1/3 I.Derived from MAGE-1/3 (174) peptide CLGLSYDGL) HWDFAWPWxxxCLGLSYDGLCLGLSYDGLxxxHWDFAWPW HWDFAWPWxxxCLGLSYDGLxxxHWDFAWPW HWDFAWPWCLGLSYDGLCLGLSYDGLHWDFAWPW HWDFAWPWCLGLSYDGLHWDFAWPW CLGLSYDGLxxxWPWAFDWHHWDFAWPWxxxCLGLSYDGLxxxWPWAFDWH CLGLSYDGLWPWAFDWHHWDFAWPWCLGLSYDGLWPWAFDWH II. Derived from MAGE-1/3 (174) (peptideCLGLSYDGLL HWDFAWPWxxxCLGLSYDGLL CLGLSYDGLLxxxHWDFAWPWHWDFAWPWxxxCLGLSYDGLLxxxHWDFAWPW HWDFAWPWCLGLSYDGLL CLGLSYDGLLHWDFAWPWHWDFAWPWCLGLSYDGLLHWDFAWPW CLGLSYDGLLxxxWPWAFDWHHWDFAWPWxxxCLGLSYDGLLxxxWPWAFDWH CLGLSYDGLLWPWAFDWHHWDFAWPWCLGLSYDGLLWPWAFDWH III. Derived from MAGE-1/3 (114) (peptideLLKYRAREPV) HWDFAWPWxxxLLKYRAREPV LLKYRAREPVxxxHWDFAWPWHWDFAWPWxxxLLKYRAREPVxxxHWDFAWPW HWDFAWPWLLKYRAREPV LLKYRAREPVHWDFAWPWHWDFAWPWLLKYRAREPVHWDFAWPW LLKYRAREPVxxxWPWAFDWHHWDFAWPWxxxLLKYRAREPVxxxWPWAFDWH LLKYRAREPVWPWAFDWHHWDFAWPWLLKYRAREPVWPWAFDWH

[0061] TABLE 7 Javelinized melanoma antigens derived from MAGE-3HWDFAWPWxxxFLWGPRALV FLWGPRALVxxxHWDFAWPWHWDFAWPWxxxFLWGPRALVxxxHWDFAWPW HWDFAWPWFLWGPRALV FLWGPRALVHWDFAWPWHWDFAWPWFLWGPRALVHWDFAWPW FLWGPRALVxxxWPWAFDWHHWDFAWPWxxxFLWGPRALVxxxWPWAFDWH FLWGPRALVWPWAFDWHHWDFAWPWFLWGPRALVWPWAFDWH

[0062] Javelinization of melanoma antigens may also incorporate CpGmotif sequences (see Krieg, 2000, Curr. Opinion Immunol. 12:35-43) atthe C-terminal end of the javelin sequence preceding the melanomaantigen. Alternatively, CpG sequences can be javelinized separately andco-administered with hsp bound non-covalently to Jav-CpG andJav-melanoma antigen. Immunotherapeutic compositions that may beadministered to the human subject may also include, in addition to hspbound non-covalently to Jav-melanoma antigen, a mixture of Jav-CpGsequences.

[0063] In further non-limiting embodiments, one or more T-helperpeptides may be linked to the antigen of interest or separatelyjavelinized and co-administered with javelinized melanoma antigen.

[0064] A javelin molecule may be covalently linked to a melanoma antigenusing any method known in the art. In determining the method of linkingto be used, particular chemical characteristics of the melanoma antigenmay favor the choice of one method over another. For example, where themelanoma antigen comprises carbohydrate groups, a carbohydrate-basedcoupling method may advantageously be used (see below).

[0065] A pamphlet published by Pierce. Chemical Company, entitled“Double Agents™ Cross-Linking Reagents Selection Guide” (published in1999, and available from Pierce Chemical Co. as Catalog #1600310)provides a useful set of criteria for selecting a proper agent includingthe following. Cross-linking reagents are identified by their acronyms,which would be recognized by the skilled artisan. Cleavable and/ornon-cleavable cross-linkers may be used. If lysines and sulfhydrylgroups are available for cross-linking, one may consider using aheterobifunctional amine/sulfhydryl reactive agent such as AMAS, BMPS,EMCS, sulfo-EMCS, GMBS, sulfo-GMBS, sulfo-KMUS, MBS, sulfo-MBS, SBAP,SIA, SIAB, sulfo-SIAB, SMCC, LC-SMCC, SMPB, SMPH, sulfo-SMPB, SVSB,BMPA, EMCA, KMUA, SMPT, sulfo-LC-SMPT, SPDP, LC-SPDP, and sulfo-LC-SPDP.If it is desirable to first react the agent with an —SH group on onemolecule (e.g., the javelin) before coupling to an NH₂ on a secondmolecule (e.g., the melanoma antigen), it may be desirable, from amongthe aforelisted agents, to use BMPA, EMCA or KMUA. If it is desirable toincorporate a carboxyl (COOH) group into one molecule (e.g., thejavelin) to facilitate coupling to the second molecule (e.g., themelanoma antigen), useful cross-linking reagents may includeheterobifunctional, sequential sulfhydryl to amine-reactive agents suchas BMPA, EMCA, or KMUA. If one of the components to be linked (e.g., themelanoma antigen) lacks reactive groups or if the presence or identityof such groups is unknown, it may be desirable to use aheterofunctional-photoreactive cross-linking agent such as ANB-NOS,NHS-ASA, sulfo-NHS-LC-ASA, sulfo-HSAB, SASD, sulfo-SAPB, SANPAH,sulfo-SANPAH, SFAD, ABH, EMCH, KMUH, M₂C₂H, MPBH, ASBA,sulfo-NHS-LC-ASA, SASD, and APDP. Additional information may be found inthe Pierce pamphlet and/or in Hermanson, 1995, “BioconjugateTechnologies”, Academic Press, Inc., Pierce Product #20002GJ, and Wong,1991, “Chemistry of Protein Conjugation and Cross-Linking, CRC Press,Inc., Pierce Product No. 15010GJ.

[0066] In one particular non-limiting set of embodiments, the presentinvention provides for covalently linking a javelin molecule containinga terminal Cys residue to a melanoma antigen comprising a terminal NH₂group (or ajavelin molecule containing a terminal NH₂ residue to amelanoma antigen comprising a terminal Cys residue) using standardtechniques, for example, using an amine-sulffiydryl cross-linker such asN-(α-maleimidodoacetoxy)-succinimide ester (“AMAS”) or “KMUS” (PierceChemical Co.). Such methods would generally involve reductivemethylation of the javelin molecule to block N-termini, cross-linking ofblocked peptide at pH 6.5-7.5 using sulfo-KMUS or AMAS, and reacting thesuccinimide group of the modified javelin with the melanoma antigen atpH 8-9. A detailed description of such a protocol may be found in PierceProduct Description No. 22295; May, 1989, Biochem 28:1718; and Satyre etal., 1984, J. Med. Chem. 27:1325.

[0067] In another non-limiting set of embodiments, the present inventionprovides for covalently linking a javelin molecule to a melanoma antigenvia a photo-reactive cross linker. An example of one such cross-linkeris N-5-azido-2-nitrobenzyloxy-succinimide (“ANB-NOS”).

[0068] In yet another non-limiting set of embodiments, the presentinvention provides for covalently linking a javelin molecule to amelanoma antigen via a method which attaches the javelin to acarbohydrate group on the melanoma antigen. Cross-linking reagents whichmay be used to effect such linkage includeN-(E-maleimidocaproicacid)hydrazide (“EMCH”), N-(K-maleimidoundecanoicacid) hyrdazide (“KMUH”), 4-(4-N-maleimidophenyl)-butyric acid hydrazideHCl (“MPBH”), “MPBA” or photoreactive agents (see Pierce Pamphlet, citedsupra).

[0069] Where one particular method of linking is appropriate to themelanoma antigen, the javelin molecule can be engineered to contain a“linker region” containing amino acid residues or other chemicalstructures which are appropriate to the selected linking method.

[0070] In yet further embodiments of the invention, a javelin moleculemay be linked to a melanoma antigen by the creation of a fusion protein,whereby a nucleic acid encoding a melanoma antigen protein or peptide islinked, in the proper reading frame, to a javelin-encoding nucleic acid.The javelin may be introduced at either terminus. Alternatively, nucleicacid may be engineered to position one or more javelin peptide withinthe body of the melanoma antigen. The nucleic acid may be used toproduce its encoded protein using standard techniques.

4.1.8. Heat Shock Proteins

[0071] The term “heat shock protein”, as used herein, refers to stressproteins (including homologs thereof expressed constitutively),including, but not limited to, gp96, hsp90, BiP, hsp70, hsp60, hsp40,hsc70, hsp170 and hsp10. Hsp target may be prepared from a naturalsource, expressed recombinantly, or chemically synthesized.

[0072] For example, cDNAs which may be used to express other heat shockproteins include, but are not limited to, gp96: human: GenebankAccession No. X15187; Maki et al., Proc. Natl. Acad. Sci. U.S.A.87:5658-5562; mouse: Genebank Accession No. M16370; Srivastava et al.,Proc. Natl. Acad. Sci. U.S.A. 84:3807-3811; BiP: human: GenebankAccession No. M19645, Ting et al., 1988, DNA 7:275-286; mouse GenebankAccession No. U16277, Haas et al., 1988, Proc. Natl. Acad. Sci. U.S.A.85:2250-2254; hsp70: human: Genebank Accession No. M24743, Hunt et al.,1985, Proc. Natl. Acad. Sci. U.S.A. 82:6455-6489; mouse: GenebankAccession No. M35021, Hunt et al., 1990, Gene 87:199-204; and hsp40:human: Genebank Accession No. D49547, Ohtsuka, 1993, Biochem. Biophys.Res. Commun. 197:235-240. Such sequences may be expressed using anyappropriate expression vector known in the art. Suitable vectorsinclude, but are not limited to, herpes simplex viral based vectors suchas pHSVI (Geller et al., 1990, Proc. Natl. Acad. Sci. U.S.A.87:8950-8954); retroviral vectors such as MFG (Jaffee et al., 1993,Cancer Res. 53:2221-2226), and in particular Moloney retroviral vectorssuch as LN, LNSX, LNCX, and LXSN (Miller and Rosman, 1989, Biotechniques7:980-989); vaccinia viral vectors such as MVA (Sutter and Moss, 1992,Proc. Natl. Acad. Sci. U.S.A. 89:10847-10851); adenovirus vectors suchas pJM17 (Ali et al., 1994, Gene Therapy 1:367-384; Berker, 1988,Biotechniques 6:616-624; Wand and Finer, 1996, Nature Medicine2:714-716); adeno-associated virus vectors such as AAV/neo (Mura-Cachoet al., 1992, J. Immunother. 11:231-237); pcDNA3 (InVitrogen); pET 11 a,pET3a, pET11d, pET3d, pET22d, and pET12a (Novagen); plasmid AH5 (whichcontains the SV40 origin and the adenovirus major late promoter);pRC/CMV (InVitrogen); pCMU II (Paabo et al., 1986, EMBO J. 5:1921-1927);pZipNeo SV (Cepko et al., 1984, Cell 37:1053-1062) and pSRα (DNAX, PaloAlto, Calif.).

[0073] A cDNA for human hsp70 may be cloned by oligonucleotide directedpolymerase chain reaction (“PCR”) from a human brain cDNA library, usingprimers designed based on the known sequence of the hsp70 gene andconsidering the vector into which it is to be inserted. For example, theresulting hsp70 cDNA may be cloned into the pET27a vector (Novagen) toform expression vector pET27hhsp70, which may be propagated so that theinserted cDNA may be sequenced. The sequence of the inserted cDNA shouldconform to the known sequence of human hsp70. Preferably, the cDNA mayencode a protein having the amino acid sequence set forth in GeneBankhaving an accession number AAD21816. Expression vector pET27hhsp70 maythen be transfected into Escherichia coli strain HMS174(DE3) (Novagen).The genotype of this strain is F⁻ recA1 hsdR (r_(K12) ⁻mK₁₂ ⁺) Rif^(R)(DE3). This strain is a K12 strain of E. coli. The resulting expressionstrain of transfected bacter may be referred to as HMS174 (DE3) hhsp70.Cells from the expression strain may be confirmed to be free of allprophage, and viability and retention of the expression construct may beconfirmed. To prepare sufficient amounts of hsp70 for clinical use, 50liters of the expression strain HMS174 (DE3) hhsp70 may be grown inanimal free medium containing 122.5 g phytone peptone, 588.0 g yeastextract, 367.5 g sodium chloride, 9.8 g methionine, and ultrapure waterto 50 liters. Before inoculation with expression strain bacteria, themedium may be sterilized, and supplemented with kanamycin to a finalconcentration of 30 micrograms per milliliter. The medium may then beinoculated with one liter of an overnight culture of the HMS174(DE3)bacteria. The pH, level of dissolved oxygen and temperature inside thefermenter reactor may be carefully monitored. When the culture reachesan optical density of approximately 1.160 (for example, approximately2.5 hours after inoculation), IPTG (isopropyl-B-D-thiogalactopyranoside;Boehringer Mannheim Corp.) may be added to a final concentration of 1 mMto initiate the induction of expression of human hsp70. Growth may thenbe continued until an optical density of approximately 2.7 is attained(for example, after an additional 3.5 hours following addition of IPTG).The fermented bacteria may then be harvested by centrifugation usingstandard techniques. The bacterial pellet may be resuspended in oneliter of buffer containing the following ingredients: 1.93 g sodiumphosphate (monobasic), 5.11 g sodium phosphate (dibasic), 1.46 g sodiumchloride, 0.74 g EDTA, 100 ml glycerol and 900 ml ultrapure water. Theresuspended bacteria may then optionally be frozen on dry ice beforefurther processing. To continue processing, the frozen bacteria may bethawed if necessary, and then may be disrupted by pressure lysis. Theresulting lysate may then be cleared and sterile filtered (and again,optionally frozen at −80° C. prior to further processing).

[0074] For example but not by way of limitation, a bacterial lysatecomprising human hsp70 may be subjected to the following three-stepprotocol to purify human hsp70. The specific example provided utilizes750 liters of lysate; adjustments may be made for different lysatevolumes. In the first step of the protocol, 750 ml. of the clearedlysate, prepared as set forth above, may be diluted two-fold with 20 mMsodium phosphate buffer pH 7.0. This 1500 ml of diluted and clearedbacterial lysate may be loaded onto a 1.9 liter column (13 cm×15 cm) ofDEAE Sephacel (Pharmacia) which has been previously equilibrated with 2column volumes of buffer A (20 mM sodium phosphate buffer 7.0, 25 mMsodium chloride, 10 mM ammonium sulfate, 1 mM DTT). After loading, thecolumn may be washed with 6 column volumes of buffer A before elution iscarried out with two column volumes of buffer B (20 mM sodium phosphatebuffer pH 7.0, 85 mM sodium chloride, 10 mM ammonium sulfate, 1 mM DTT).Somewhat less than 4 liters of eluate (e.g. 3.8 liters) may be expectedto be recovered. The eluate may then be diafiltered (buffer exchanged)against a 10-fold volume (e.g., 38 liters for 3.8 liters of eluate) ofbuffer C (20 mM sodium citrate pH 6.0, 85 mM sodium chloride, 10 mMammonium sulfate, 1 mM DTT).

[0075] In the second step of the protocol, a column having one tenth thevolume of eluate (e.g., 380 ml, 9 cm×6.1 cm) of Q-sepharose fast flow(Pharmacia) may be equilibrated with one column volume of buffer C(supra). The buffer exchanged eluate (e.g., 380 ml) from the DEAE columnmay then be run over the Q-sepharose column, and the flow through may becollected (e.g., 4.18 liters). The purpose of this column is to reduceor eliminate the endotoxin content of the hsp70 being purified.

[0076] In the third step of the protocol, a 700 ml column (13 cm×5.5 cm)of custom cGMP ATP agarose (Sigma-Aldrich Fine Chemicals) may beequilibrated in one column volume of buffer D (20 mM sodium citrate pH6.0, 85 mM sodium chloride, 10 mM ammonium sulfate). To the eluate fromthe Q-sepharose column (e.g. 4.18 liters) magnesium acetate may be addedto a final concentation of 0.25 mM, and the resulting solution may berun over the ATP agarose column. The column may then be washed with sixcolumn volumes of buffer D and finally eluted with 2 column volumes ofbuffer E (20 mM sodium citrate pH 6.0, 85 mM sodium chloride, 10 mMammonium sulfate, 1 mM magnesium acetate, 1 mM adenosine triphosphate(ATP)). The eluted material, which may be reasonably expected to behuman hsp70 having a purity of greater than 95 percent) may be bufferexchanged into phosphate buffered saline and concentrated to a finalconcentration of 10-20 mg/ml, and then sterile filtered.

4.1.9. Complexes of Javelinized Melanoma Antigens and Heat ShockProteins

[0077] In one set of embodiments of the invention, a single javelinizedmelanoma antigen may be bound to a single heat shock protein or,alternatively, to a plurality of heat shock proteins. In another set ofembodiments of the invention, a plurality of javelinized melanomaantigens can be bound to a single heat shock protein or, alternatively,to a plurality of heat shock proteins. Further, in nonlimitingembodiments of the invention, different javelinized melanoma antigensand different types of heat shock protein may be combined; for example,javelinized gp100 and tyrosinase derived peptides may be complexed withhsp70, or javelinized gp100 peptide may be complexed with hsp70 andgp96, or javelinized gp100 and tyrosinase peptides may be complexed withhsp70 and gp96, in the same formulation. Analogous combinations may bemade using other javelinized melanoma antigens and heat shock proteins.

[0078] Complexes between javelinized melanoma antigens and heat shockproteins can be generated by a variety of methods. In one embodiment,javelinized melanoma antigen(s) can be combined with heat shockprotein(s) at molar ratios from 0.01:1 to 100:1, and preferably at molarratios from 0.1:1 to 10:1, of Jav-antigen:heat shock protein, and atweight/volume ratios of from 1:1000 to 1:1. The molecules may becombined in an aqueous solution that is buffered in the range between pH4.5 and pH 9 and more preferably in the range pH 6 to pH 8. Examples ofbuffering compounds include Tris based buffer, phosphate based buffers,bicarbonate based buffers, and succinate based buffers. Theconcentrations of these buffering compounds range from, but are notlimited to, 1 mM to 500 mM, and more preferably range from 10 mM to 200mM.

[0079] Salts may also be added to the complex formation solution. Thesesalts include but are not restricted to sodium chloride, potassiumchloride, ammonium chloride, ammonium sulfate, magnesium chloride,magnesium acetate, potassium acetate, sodium acetate, and combinationsthereof. The concentrations of these salts may fall in the ranges of,but are not limited to, 0.1 micromolar to 500 mM, and more preferably 20mM to 200 mM.

[0080] Other compounds that may be added to the complex formationsolution include adenosine 5′ diphosphate (ADP) and analogues thereofand DMSO. Such compounds may be added at concentrations ranging from,but not limited to, 0.001 mM to 500 mM, and more preferably 0.1 mM to100 mM.

[0081] The reactants may then be incubated at a temperature rangingfrom, but not limited to 4° C. to 65° C., more preferably from 20° C. to55° C. This incubation may be carried out for a time period rangingfrom, but not limited to 1 minute to 4 hours, more preferably from 20minutes to 1 hour.

[0082] As one non-limiting example, heat shock protein and peptide maybe introduced into a solution to produce a 1:10 molar ratio (heat shockprotein:peptide) in a buffer containing 1 mM magnesium acetate (ormagnesium chloride) and 1 mM ADP. The mixture may then be incubated at25° C. for about 1 hour and subsequently centrifuged to remove anyaggregates. The resulting solution may then be sterile filtered. Ofnote, the buffer of choice can vary depending upon the optimalconditions identified in biochemical analysis. For example, a suitablebuffer may be a Tris buffer with a pH range from 7-8 containing NaCl ata concentration of 20 mM-100 mM and DMSO at a concentration of 1.0%. Acomplex prepared as set forth above may be frozen in a dry ice/ethanolbath and stored at −80° C.

[0083] In another non-limiting example, purified heat shock protein(e.g. the human hsp70) may be complexed with one or more javelinizedmelanoma antigen(s) by combining heat shock protein at a concentrationof 0.25 mg/ml with either 0.25, 0.025 or 0.0025 mg/ml of thejavelinizedmelanoma antigen(s) in a buffer comprising 25 mM Tris (THAM), 50 mMNaCl, 5 mM MgCl₂, 1 mM ADP, brought to pH 8.0 with acetic acid.

[0084] In another non-limiting example, heat shock protein and one ormore javelinized melanoma antigen may be combined as follows: 0.25 mg/mlheat shock protein may be combined with 0.25 mg/ml javelinized melanomaantigen in 25 mM Tris (Tris) pH 8.0, 50 mM NaCl, 5 mM MgCl₂, 6.7 mMAcetate, 1 mM ADP, 0.26 mM KCl, 0.518 mM Na₂HPO₄, 0.173 mM KH₂PO₄, and afinal DMSO concentration of 1%.

[0085] In another specific, non-limiting embodiment of the invention,human hsp70 at a concentration of 0.25 mg/ml may be incubated with 0.25mg/ml, 0.025 mg/ml, or 0.0025 mg/ml of Jav-tyrosinase peptide (368-377),YMDGTMSQVGSGHWDFAWPW (SEQ ID NO: 209) in a buffer comprising 25 mM Tris(THAM), 50 mM NaCl, 5 mM MgCl₂, and 1 mM ADP, with the pH brought to 8.0with acetic acid.

[0086] In yet another specific, non-limiting embodiment of theinvention, human hsp70 at a concentration of 0.25 mg/ml may be incubatedwith 0.25 mg/ml, 0.025 mg/ml, or 0.0025 mg/ml of Jav-gp100 peptide(209-217) IMDQVPFSVGSGHWDFAWPW (SEQ ID NO: 245) in a buffer comprising25 mM Tris (THAM), 50 mM NaCl, 5 mM MgCl₂, and 1 mM ADP, with the pHbrought to 8.0 with acetic acid.

4.2 Administration of the Immunotherapeutic Complexes

[0087] The heat shock protein/Jav-antigen complexes of the invention maybe administered in therapeutic amounts to subjects in need of suchtreatment. Subjects in need of such treatment include subjects sufferingfrom melanoma, who have previously been diagnosed with melanoma, or whoare at risk for developing melanoma (for example, persons with a familyhistory of melanoma, with sun-sensitive skin, or with sun-damaged skin).Patients having a diagnosis of melanoma in situ, AJCC Stage I, or moreadvanced stages of melanoma (e.g. AJCC Stage II, III, or IV) may betreated according to the invention. HLA restriction of Jav-melanomaantigen should be considered in identifying subjects suitable fortreatment, as those subjects should be of the HLA type to which responseis restricted.

[0088] In nonlimiting embodiments, the likelihood that a subjectsuffering from or having previously been diagnosed with melanoma willrespond to therapy according to the invention may be evaluated bydetermining whether the melanoma cells of the subject carry a particularmelanoma antigen. The evaluation may also be made in a subject suspectedof suffering from melanoma. Such an evaluation may be made, for example,by RT-PCR analysis as described in Berking et al., 1999, Arch. Dermatol.Res. 291(9):479-484 and Riker et al., 2000, Int. J. Cancer86(6):818-826, which report that tumor markers for melanoma could bedetected in the peripheral blood of melanoma patients.

[0089] Heat shock protein/Jav-Antigen is administered in an amounteffective in inducing or maintaining a therapeutic immune response. A“therapeutic immune response” refers to an increase in humoral and/orcellular immunity directed toward melanoma cells and which is minimallyor non-cross reactive with non-malignant cells, of a magnitudesufficient to protect against the development, growth and/or spread ofmelanoma cells in a patient. Preferably, but not by way of limitation,the induced level of immunity (humoral or cellular) directed toward themelanoma antigen is at least four fold, and preferably at least 16-foldgreater than the levels of immunity directed toward the antigen prior tothe administration of the immunotherapeutic composition.

[0090] The level of immunity may be measured by any method known in theart. The immune response may be measured qualitatively in vivo, whereinan arrest in progression or a remission of melanoma in the subject isconsidered to indicate the induction of a therapeutic immune response.As another example of a means for determining, in vivo, whether atherapeutic immune response has occurred, skin tests for delayedhypersensitivity responses may be performed, which may, e.g. utilize0.05 ml volumes containing 10 μg melanoma antigen. Tests may be appliedintradermally at suitable time points in the treatment, for example,prior to the first vaccination and after the final immunizations and areread at 48 hours. The presence of a response is a positive indicationthat a therapeutic immune response toward the javelinized melanomaantigens is being induced in the subject.

[0091] Alternatively, the immune response may be evaluated by laboratorytests. as one non-limiting example, humoral immunity may be evaluated bymeasuring antibody titers. Other examples of suitable tests includeELISPOT assays, proliferation assays, and/or cytokine release assays,which may be performed as described in Lewis et al., 1999, Int. J.Cancer 87(3:391-398), which is incorporated by reference. Tetramerassays may also or alternatively be used to measure specificallyreactive T cells against melanoma antigen, as described in Jaeger, E. etal., 1996, Int. J. Cancer 66: 162-169. An additional test which may beused singly or in combination with the above is the chromium releaseassay, as described in Wu, J. Y. et al., 1992, J. Immunol. 148:1519-1525, in which a panel of HLA typed melanoma cell lines are used.Many of the cell lines have been studied extensively for expression of avariety of tyrosinase and gp100 antigens. For example, SK MEL 29 whichis HLA A2+, expresses both the tyrosinase and gp100 antigens.Lymphocytes from the patient from whom SK MEL 29 was derived recognizetyrosinase strongly and can serve as a positive control. (Nestle et al.,1998, Nature Medicine 4: 328-332; Rosenberg et al., 1998, NatureMedicine 4:321-327).

[0092] In particular nonlimiting embodiments of the invention, theimmunotherapeutic composition comprises, for each javelinized melanomaantigen, between 1 to 100 μg of the javelinized melanoma antigen and 100μg of heat shock protein, such as hsp70, delivered in a volume of 0.4 mlof a 25 mM Tris (THAM) buffer containing 50 mM NaCl, 5 mM MgCl₂, 6.7 mMacetate, 1 mM ADP, 0.26 mM KCl, 0.518 mM Na₂HPO₄, 1 percent DMSO and hasa pH of 8.00.

[0093] In one group of specific, non-limiting embodiments of theinvention, a complex between human hsp70 and Jav-tyrosinasepeptide(368-377) may be prepared as set forth in the preceding sectionand administered such that a patient receives 100 ricrograms of hsp70with 1, 10 or 100 micrograms of Jav-tyrosinase peptide in a volume of0.4 ml of buffer containing 50 mM NaCl, 5 mM MgCl₂, 6.7 mM acetate, 1 mMADP, 0.26 mM KCl, 0.518 mM Na₂HPO₄, 1 percent DMSO and has apH of 8.00.

[0094] In a second group of specific, non-limiting embodiments of theinvention, a complex between human hsp70 and Jav-gp100 peptide(209-217)may be prepared as set forth in the preceding section and administeredsuch that a patient receives 100 micrograms of hsp70 with 1, 10 or 100micrograms of Jav-gp100 peptide in a volume of 0.4 ml of buffercontaining 50 mM NaCl, 5 mM MgCl₂, 6.7 mM acetate, 1 mM ADP, 0.26 mMKCl, 0.518 mM Na₂HPO₄, 1 percent DMSO and has a pH of 8.00.

[0095] In a third group of specific, non-limiting embodiments of theinvention, a complexes between human hsp70 and Jav-tyrosinasepeptide(368-377) and between human hsp70 and Jav-gp100 peptide (209-217)may be prepared as set forth in the preceding section and administeredsuch that a patient receives 200 micrograms of hsp70 with 1, 10 or 100micrograms of Jav-tyrosinase peptide and of Jav-gp100 peptide in avolume of 0.8 ml of buffer containing 50 mM NaCl, 5 mM MgCl₂, 6.7 mMacetate, 1 mM ADP, 0.26 mM KCl, 0.518 mM Na₂HPO₄, 1 percent DMSO and hasa pH of 8.00.

[0096] An immunotherapeutic composition according to the invention maybe initially a freeze-dried or lyophilized preparation of complex towhich buffer solution is added. Alternatively, the immunotherapeuticcomposition may be delivered as a dry powder formulation. Furtherformulations, such as sustained release preparations, microsphere orliposome based preparations, etc. may also be used, which are preparedusing techniques that are known in the art.

[0097] Immunization may be delivered in an inpatient or outpatientsetting. Preferably, a plurality of vaccinations are provided at regulartime intervals to optimize and sustain the immune response. In onepreferred embodiment, a human subject may receive a total of at least 5vaccinations. With regard to the time interval between vaccinations, theimmunotherapeutic composition may administered at weekly intervals, atbi-weekly intervals, or a combination of both. As another example, theimmunotherapeutic composition may be administered at weeks 0, 1, 2, 6,and 18. In another example, the second and third vaccinations may beadministered up to one week, and the fourth and fifth vaccinations, canbe administered up to two weeks, earlier or later.

[0098] Immunization can be carried out by any route known in the medicalart, including, but not limited to, intradermal, subcutaneous,intraperitoneal, intrathecal, intravenous, or intramuscular injection,or mucosal, intratracheal, or oral administration. In one preferredspecific embodiment, the immunotherapeutic composition may beadministered subcutaneously in a volume of 0.8 ml normal saline Thesites of immunization can be the same or be varied. For example, thevaccine may be administered on the arm, leg, or belly, or on anycombination thereof. For example, the first administration may be on theright arm, second administration the left arm, the third administrationon the right thigh, the fourth administration on the left thigh, thefifth on the right side of the belly and the sixth on the left side ofthe belly.

[0099] The present invention further provides for administration ofadditional biologically active agents either concurrently with or beforeor after administration of the immunotherapeutic hsp/Jav-peptidecomposition. Examples of suitable biologically active agents include butare not limited to cytokines, such as interleukin-2 (IL-2),granulocyte/macrophage colony stimulating factor (GM-CSF), interferonα2b, interferon γ, and/or a lymphokine.

[0100] In another set of nonlimiting embodiments, the present inventionprovides for methods comprising contacting patient-derived antigenpresenting cells with javelinized melanoma antigens bound to heat shockproteins in vitro, followed by re-administration of the antigenpresenting cells into the patient. For example, approximately 2-3×10⁶dendritic cells prepared from 50 mls of peripheral blood using“Lymphoprep” (GIBCO BRL, Baithersburg, Md.) may be “loaded” with heatshock protein/Jav-antigen prior to administration to a patient. Theadministration of the antigen presenting cells sensitized with theimmunotherapeutic composition may occur before, concurrent with or afterthe administration to the patient of the javelizined antigens bound tothe heat shock, proteins or other molecular chaperones at the definedweekly intervals. The antigen presenting cells can be autologous orheterologous immune cells such as cytotoxic T-lymphocytes,B-lymphocytes, and preferably macrophages and more preferably dendriticcells.

[0101] In a patient treated according to the invention, it is desirableto monitor the patient for autoimmune or hypersensitivity reactions tocomponents of the vaccine. Such reactions are theoretical possibilitiesbecause melanocyte differentiation antigens such as tyrosinase and gp100are present in the melanosomes of pigmented cells in the skin, retina,and uvea. Induction of immunity against these antigens might thereforeinduce destruction of pigmented cells, resulting in vitiligo. It is alsopossible that choroiditits could be induced. However, in patientsimmunized with gp100 or tyrosinase peptides in trials conducted atMSKCC, National Cancer Institute (NCI) and the University of Pittsburgh,there have been no reported cases of treatment related retinopathy asdetected by slit-lamp examinations. Nevertheless, it may be desirable tomonitor patients by slit-lamp ophthalmic examination.

[0102] While the invention has been described in connection with what ispresently considered to be the most practical and preferred embodiment,it will be apparent to one skilled in the art that various changes andmodifications can be made therein. Thus, the present invention is not tobe limited to the disclosed embodiments, but on the contrary, isintended to cover various modifications and equivalent arrangementsincluded within the spirit and scope of the appended claims.

[0103] Various references are cited herein, the contents of which arehereby incorporated by reference in their entireties

0 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 502 <210> SEQ ID NO 1<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 1 Tyr Met Asn Gly Thr Met Ser Gln Val 1 5 <210> SEQ ID NO 2<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 2 Met Leu Leu Ala Val Leu Tyr Val Leu 1 5 <210> SEQ ID NO 3<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 3 Tyr Met Asp Gly Thr Met Ser Gln Val 1 5 <210> SEQ ID NO 4<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 4 Met Ser Leu Gln Arg Gln Phe Leu Arg 1 5 <210> SEQ ID NO 5<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 5 Ser Val Tyr Asp Phe Phe Val Trp Leu 1 5 <210> SEQ ID NO 6<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 6 Leu Leu Gly Pro Gly Arg Pro Tyr Arg 1 5 <210> SEQ ID NO 7<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 7 Ser Leu Asp Asp Tyr Asn His Leu Val 1 5 <210> SEQ ID NO 8<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 8 Thr Leu Asp Ser Gln Val Met Ser Leu 1 5 <210> SEQ ID NO 9<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 9 Val Met Gly Thr Leu Val Ala Leu Val 1 5 <210> SEQ ID NO 10<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 10 Ile Thr Asp Gln Val Pro Phe Ser Val 1 5 <210> SEQ ID NO 11<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 11 Thr Ile Thr Asp Gln Val Pro Phe Ser Val 1 5 10 <210> SEQ IDNO 12 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 12 Tyr Leu Glu Pro Gly Val Thr Val Ala 1 5 <210> SEQ ID NO 13<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 13 Tyr Leu Glu Pro Gly Val Thr Val Ala 1 5 <210> SEQ ID NO 14<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 14 Lys Thr Trp Gly Gln Tyr Trp Gln Val 1 5 <210> SEQ ID NO 15<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 15 Thr Trp Gly Gln Tyr Trp Gln Val Leu 1 5 <210> SEQ ID NO 16<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 16 Val Leu Lys Arg Cys Leu Leu His Leu 1 5 <210> SEQ ID NO 17<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 17 Leu Asn Val Ser Leu Ala Asp Thr Asn 1 5 <210> SEQ ID NO 18<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400>SEQUENCE: 18 Ser Leu Ala Asp Thr Asn Ser Leu Ala Val 1 5 10 <210> SEQ IDNO 19 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Homo sapiens<400> SEQUENCE: 19 Leu Leu Asp Gly Thr Ala Thr Leu Arg Leu 1 5 10 <210>SEQ ID NO 20 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Homosapiens <400> SEQUENCE: 20 Val Leu Tyr Arg Tyr Gly Ser Phe Ser Val 1 510 <210> SEQ ID NO 21 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <400> SEQUENCE: 21 Ala Leu Asp Gly Gly Asn Lys His Phe Leu1 5 10 <210> SEQ ID NO 22 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <400> SEQUENCE: 22 Val Leu Pro Ser Pro Ala CysGln Leu Val 1 5 10 <210> SEQ ID NO 23 <211> LENGTH: 9 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <400> SEQUENCE: 23 Ile Met Asp Gln Val ProPhe Ser Val 1 5 <210> SEQ ID NO 24 <211> LENGTH: 9 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <400> SEQUENCE: 24 Ala Ala Gly Ile Gly Ile LeuThr Val 1 5 <210> SEQ ID NO 25 <211> LENGTH: 9 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <400> SEQUENCE: 25 Ile Leu Thr Val Ile Leu GlyVal Leu 1 5 <210> SEQ ID NO 26 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <400> SEQUENCE: 26 Glu Ala Ala Gly Ile Gly IleLeu Thr Val 1 5 10 <210> SEQ ID NO 27 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <400> SEQUENCE: 27 Ala Ala Gly Ile Gly IleLeu Thr Val Ile 1 5 10 <210> SEQ ID NO 28 <211> LENGTH: 9 <212> TYPE:PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 28 Ala Leu Glu Ala GlnGln Glu Ala Leu 1 5 <210> SEQ ID NO 29 <211> LENGTH: 9 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <400> SEQUENCE: 29 Ile Leu Glu Ser Leu PheArg Ala Val 1 5 <210> SEQ ID NO 30 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <400> SEQUENCE: 30 Ser Leu His Cys Lys ProGlu Glu Ala Leu 1 5 10 <210> SEQ ID NO 31 <211> LENGTH: 10 <212> TYPE:PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 31 Pro Leu Val Leu GlyThr Leu Glu Glu Val 1 5 10 <210> SEQ ID NO 32 <211> LENGTH: 9 <212>TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 32 Cys Leu GlyLeu Ser Tyr Asp Gly Leu 1 5 <210> SEQ ID NO 33 <211> LENGTH: 10 <212>TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 33 Leu Leu LysTyr Arg Ala Arg Glu Pro Val 1 5 10 <210> SEQ ID NO 34 <211> LENGTH: 9<212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 34 Phe LeuTrp Gly Pro Arg Ala Leu Val 1 5 <210> SEQ ID NO 35 <211> LENGTH: 9 <212>TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 35 Glu Ala AspPro Thr Gly His Ser Tyr 1 5 <210> SEQ ID NO 36 <211> LENGTH: 8 <212>TYPE: PRT <213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 36 HisTrp Asp Phe Ala Trp Pro Trp 1 5 <210> SEQ ID NO 37 <211> LENGTH: 8 <212>TYPE: PRT <213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 37 PheTrp Gly Leu Trp Pro Trp Glu 1 5 <210> SEQ ID NO 38 <211> LENGTH: 5 <212>TYPE: PRT <213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 38 GlnLys Arg Ala Ala 1 5 <210> SEQ ID NO 39 <211> LENGTH: 5 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 39 Arg Arg Arg AlaAla 1 5 <210> SEQ ID NO 40 <211> LENGTH: 5 <212> TYPE: PRT <213>ORGANISM: m13 coliphage insert <400> SEQUENCE: 40 Lys Phe Glu Arg Gln 15 <210> SEQ ID NO 41 <211> LENGTH: 8 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 41 Arg Gly Tyr Val Tyr Gln Gly Leu 1 5<210> SEQ ID NO 42 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 42 Tyr Thr Leu Val Gln Pro Leu 1 5<210> SEQ ID NO 43 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 43 Thr Pro Asp Ile Thr Pro Lys 1 5<210> SEQ ID NO 44 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 44 Thr Tyr Pro Asp Leu Arg Tyr 1 5<210> SEQ ID NO 45 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 45 Asp Arg Thr His Ala Thr Ser 1 5<210> SEQ ID NO 46 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 46 Met Ser Thr Thr Phe Tyr Ser 1 5<210> SEQ ID NO 47 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 47 Tyr Gln His Ala Val Gln Thr 1 5<210> SEQ ID NO 48 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 48 Phe Pro Phe Ser Ala Ser Thr 1 5<210> SEQ ID NO 49 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 49 Ser Ser Phe Pro Pro Leu Asp 1 5<210> SEQ ID NO 50 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 50 Met Ala Pro Ser Pro Pro His 1 5<210> SEQ ID NO 51 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 51 Ser Ser Phe Pro Asp Leu Leu 1 5<210> SEQ ID NO 52 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 52 His Ser Tyr Asn Arg Leu Pro 1 5<210> SEQ ID NO 53 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 53 His Leu Thr His Ser Gln Arg 1 5<210> SEQ ID NO 54 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 54 Gln Ala Ala Gln Ser Arg Ser 1 5<210> SEQ ID NO 55 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 55 Phe Ala Thr His His Ile Gly 1 5<210> SEQ ID NO 56 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 56 Ser Met Pro Glu Pro Leu Ile 1 5<210> SEQ ID NO 57 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 57 Ile Pro Arg Tyr His Leu Ile 1 5<210> SEQ ID NO 58 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 58 Ser Ala Pro His Met Thr Ser 1 5<210> SEQ ID NO 59 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 59 Lys Ala Pro Val Trp Ala Ser 1 5<210> SEQ ID NO 60 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 60 Leu Pro His Trp Leu Leu Ile 1 5<210> SEQ ID NO 61 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 61 Ala Ser Ala Gly Tyr Gln Ile 1 5<210> SEQ ID NO 62 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 62 Val Thr Pro Lys Thr Gly Ser 1 5<210> SEQ ID NO 63 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 63 Glu His Pro Met Pro Val Leu 1 5<210> SEQ ID NO 64 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 64 Val Ser Ser Phe Val Thr Ser 1 5<210> SEQ ID NO 65 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 65 Ser Thr His Phe Thr Trp Pro 1 5<210> SEQ ID NO 66 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 66 Gly Gln Trp Trp Ser Pro Asp 1 5<210> SEQ ID NO 67 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 67 Gly Pro Pro His Gln Asp Ser 1 5<210> SEQ ID NO 68 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 68 Asn Thr Leu Pro Ser Thr Ile 1 5<210> SEQ ID NO 69 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 69 His Gln Pro Ser Arg Trp Val 1 5<210> SEQ ID NO 70 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 70 Tyr Gly Asn Pro Leu Gln Pro 1 5<210> SEQ ID NO 71 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 71 Phe His Trp Trp Trp Gln Pro 1 5<210> SEQ ID NO 72 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 72 Ile Thr Leu Lys Tyr Pro Leu 1 5<210> SEQ ID NO 73 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 73 Phe His Trp Pro Trp Leu Phe 1 5<210> SEQ ID NO 74 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 74 Thr Ala Gln Asp Ser Thr Gly 1 5<210> SEQ ID NO 75 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 75 Phe His Trp Trp Trp Gln Pro 1 5<210> SEQ ID NO 76 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 76 Phe His Trp Trp Asp Trp Trp 1 5<210> SEQ ID NO 77 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 77 Glu Pro Phe Phe Arg Met Gln 1 5<210> SEQ ID NO 78 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 78 Thr Trp Trp Leu Asn Tyr Arg 1 5<210> SEQ ID NO 79 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 79 Phe His Trp Trp Trp Gln Pro 1 5<210> SEQ ID NO 80 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 80 Gln Pro Ser His Leu Arg Trp 1 5<210> SEQ ID NO 81 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 81 Ser Pro Ala Ser Pro Val Tyr 1 5<210> SEQ ID NO 82 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 82 Phe His Trp Trp Trp Gln Pro 1 5<210> SEQ ID NO 83 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 83 His Pro Ser Asn Gln Ala Ser 1 5<210> SEQ ID NO 84 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 84 Asn Ser Ala Pro Arg Pro Val 1 5<210> SEQ ID NO 85 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 85 Gln Leu Trp Ser Ile Tyr Pro 1 5<210> SEQ ID NO 86 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 86 Ser Trp Pro Phe Phe Asp Leu 1 5<210> SEQ ID NO 87 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 87 Asp Thr Thr Leu Pro Leu His 1 5<210> SEQ ID NO 88 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 88 Trp His Trp Gln Met Leu Trp 1 5<210> SEQ ID NO 89 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 89 Asp Ser Phe Arg Thr Pro Val 1 5<210> SEQ ID NO 90 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 90 Thr Ser Pro Leu Ser Leu Leu 1 5<210> SEQ ID NO 91 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 91 Ala Tyr Asn Tyr Val Ser Asp 1 5<210> SEQ ID NO 92 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 92 Arg Pro Leu His Asp Pro Met 1 5<210> SEQ ID NO 93 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 93 Trp Pro Ser Thr Thr Leu Phe 1 5<210> SEQ ID NO 94 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 94 Ala Thr Leu Glu Pro Val Arg 1 5<210> SEQ ID NO 95 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 95 Ser Met Thr Val Leu Arg Pro 1 5<210> SEQ ID NO 96 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 96 Gln Ile Gly Ala Pro Ser Trp 1 5<210> SEQ ID NO 97 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 97 Ala Pro Asp Leu Tyr Val Pro 1 5<210> SEQ ID NO 98 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 98 Arg Met Pro Pro Leu Leu Pro 1 5<210> SEQ ID NO 99 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 99 Ala Lys Ala Thr Pro Glu His 1 5<210> SEQ ID NO 100 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 100 Thr Pro Pro Leu Arg Ile Asn 1 5<210> SEQ ID NO 101 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 101 Leu Pro Ile His Ala Pro His 1 5<210> SEQ ID NO 102 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 102 Asp Leu Asn Ala Tyr Thr His 1 5<210> SEQ ID NO 103 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 103 Val Thr Leu Pro Asn Phe His 1 5<210> SEQ ID NO 104 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 104 Asn Ser Arg Leu Pro Thr Leu 1 5<210> SEQ ID NO 105 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 105 Tyr Pro His Pro Ser Arg Ser 1 5<210> SEQ ID NO 106 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 106 Gly Thr Ala His Phe Met Tyr 1 5<210> SEQ ID NO 107 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 107 Tyr Ser Leu Leu Pro Thr Arg 1 5<210> SEQ ID NO 108 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 108 Leu Pro Arg Arg Thr Leu Leu 1 5<210> SEQ ID NO 109 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 109 Thr Ser Thr Leu Leu Trp Lys 1 5<210> SEQ ID NO 110 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 110 Thr Ser Asp Met Lys Pro His 1 5<210> SEQ ID NO 111 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 111 Thr Ser Ser Tyr Leu Ala Leu 1 5<210> SEQ ID NO 112 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 112 Asn Leu Tyr Gly Pro His Asp 1 5<210> SEQ ID NO 113 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 113 Leu Glu Thr Tyr Thr Ala Ser 1 5<210> SEQ ID NO 114 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 114 Ala Tyr Lys Ser Leu Thr Gln 1 5<210> SEQ ID NO 115 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 115 Ser Thr Ser Val Tyr Ser Ser 1 5<210> SEQ ID NO 116 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 116 Glu Gly Pro Leu Arg Ser Pro 1 5<210> SEQ ID NO 117 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 117 Thr Thr Tyr His Ala Leu Gly 1 5<210> SEQ ID NO 118 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 118 Val Ser Ile Gly His Pro Ser 1 5<210> SEQ ID NO 119 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 119 Thr His Ser His Arg Pro Ser 1 5<210> SEQ ID NO 120 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 120 Ile Thr Asn Pro Leu Thr Thr 1 5<210> SEQ ID NO 121 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 121 Ser Ile Gln Ala His His Ser 1 5<210> SEQ ID NO 122 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 122 Leu Asn Trp Pro Arg Val Leu 1 5<210> SEQ ID NO 123 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 123 Tyr Tyr Tyr Ala Pro Pro Pro 1 5<210> SEQ ID NO 124 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 124 Ser Leu Trp Thr Arg Leu Pro 1 5<210> SEQ ID NO 125 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 125 Asn Val Tyr His Ser Ser Leu 1 5<210> SEQ ID NO 126 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 126 Asn Ser Pro His Pro Pro Thr 1 5<210> SEQ ID NO 127 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 127 Val Pro Ala Lys Pro Arg His 1 5<210> SEQ ID NO 128 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 128 His Asn Leu His Pro Asn Arg 1 5<210> SEQ ID NO 129 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 129 Tyr Thr Thr His Arg Trp Leu 1 5<210> SEQ ID NO 130 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 130 Ala Val Thr Ala Ala Ile Val 1 5<210> SEQ ID NO 131 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 131 Thr Leu Met His Asp Arg Val 1 5<210> SEQ ID NO 132 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 132 Thr Pro Leu Lys Val Pro Tyr 1 5<210> SEQ ID NO 133 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 133 Phe Thr Asn Gln Gln Tyr His 1 5<210> SEQ ID NO 134 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 134 Ser His Val Pro Ser Met Ala 1 5<210> SEQ ID NO 135 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 135 His Thr Thr Val Tyr Gly Ala 1 5<210> SEQ ID NO 136 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 136 Thr Glu Thr Pro Tyr Pro Thr 1 5<210> SEQ ID NO 137 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 137 Leu Thr Thr Pro Phe Ser Ser 1 5<210> SEQ ID NO 138 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 138 Gly Val Pro Leu Thr Met Asp 1 5<210> SEQ ID NO 139 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 139 Lys Leu Pro Thr Val Leu Arg 1 5<210> SEQ ID NO 140 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 140 Cys Arg Phe His Gly Asn Arg 1 5<210> SEQ ID NO 141 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 141 Tyr Thr Arg Asp Phe Glu Ala 1 5<210> SEQ ID NO 142 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 142 Ser Ser Ala Ala Gly Pro Arg 1 5<210> SEQ ID NO 143 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <400> SEQUENCE: 143 Ser Leu Ile Gln Tyr Ser Arg 1 5<210> SEQ ID NO 144 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13coliphage insert <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(7)...(7) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 144 Asp Ala Leu Met Trp Pro Xaa 1 5 <210> SEQ ID NO 145 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (3)...(3) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 145 Ser Ser Xaa SerLeu Tyr Ile 1 5 <210> SEQ ID NO 146 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 146 Phe Asn Thr SerThr Arg Thr 1 5 <210> SEQ ID NO 147 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 147 Thr Val Gln HisVal Ala Phe 1 5 <210> SEQ ID NO 148 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 148 Asp Tyr Ser PhePro Pro Leu 1 5 <210> SEQ ID NO 149 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 149 Val Gly Ser MetGlu Ser Leu 1 5 <210> SEQ ID NO 150 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (2)...(2) <223> OTHER INFORMATION: Any aminoacid residue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(6)...(6) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 150 Phe Xaa Pro Met Ile Xaa Ser 1 5 <210> SEQ ID NO 151 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 151 Ala Pro Pro Arg Val Thr Met 1 5 <210> SEQ ID NO 152 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 152 Ile Ala Thr Lys Thr Pro Lys 1 5 <210> SEQ ID NO 153 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 153 Lys Pro Pro Leu Phe Gln Ile 1 5 <210> SEQ ID NO 154 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 154 Tyr His Thr Ala His Asn Met 1 5 <210> SEQ ID NO 155 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 155 Ser Tyr Ile Gln Ala Thr His 1 5 <210> SEQ ID NO 156 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 156 Ser Ser Phe Ala Thr Phe Leu 1 5 <210> SEQ ID NO 157 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 157 Thr Thr Pro Pro Asn Phe Ala 1 5 <210> SEQ ID NO 158 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 158 Ile Ser Leu Asp Pro Arg Met 1 5 <210> SEQ ID NO 159 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 159 Ser Leu Pro Leu Phe Gly Ala 1 5 <210> SEQ ID NO 160 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 160 Asn Leu Leu Lys Thr Thr Leu 1 5 <210> SEQ ID NO 161 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 161 Asp Gln Asn Leu Pro Arg Arg 1 5 <210> SEQ ID NO 162 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 162 Ser His Phe Glu Gln Leu Leu 1 5 <210> SEQ ID NO 163 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 163 Thr Pro Gln Leu His His Gly 1 5 <210> SEQ ID NO 164 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 164 Ala Pro Leu Asp Arg Ile Thr 1 5 <210> SEQ ID NO 165 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 165 Phe Ala Pro Leu Ile Ala His 1 5 <210> SEQ ID NO 166 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 166 Ser Trp Ile Gln Thr Phe Met 1 5 <210> SEQ ID NO 167 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 167 Asn Thr Trp Pro His Met Tyr 1 5 <210> SEQ ID NO 168 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 168 Glu Pro Leu Pro Thr Thr Leu 1 5 <210> SEQ ID NO 169 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 169 His Gly Pro His Leu Phe Asn 1 5 <210> SEQ ID NO 170 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 170 Tyr Leu Asn Ser Thr Leu Ala 1 5 <210> SEQ ID NO 171 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 171 His Leu His Ser Pro Ser Gly 1 5 <210> SEQ ID NO 172 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 172 Thr Leu Pro His Arg Leu Asn 1 5 <210> SEQ ID NO 173 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 173 Ser Ser Pro Arg Glu Val His 1 5 <210> SEQ ID NO 174 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 174 Asn Gln Val Asp Thr Ala Arg 1 5 <210> SEQ ID NO 175 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 175 Tyr Pro Thr Pro Leu Leu Thr 1 5 <210> SEQ ID NO 176 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 176 His Pro Ala Ala Phe Pro Trp 1 5 <210> SEQ ID NO 177 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 177 Leu Leu Pro His Ser Ser Ala 1 5 <210> SEQ ID NO 178 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 178 Leu Glu Thr Tyr Thr Ala Ser 1 5 <210> SEQ ID NO 179 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 179 Lys Tyr Val Pro Leu Pro Pro 1 5 <210> SEQ ID NO 180 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 180 Ala Pro Leu Ala Leu His Ala 1 5 <210> SEQ ID NO 181 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 181 Tyr Glu Ser Leu Leu Thr Lys 1 5 <210> SEQ ID NO 182 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 182 Ser His Ala Ala Ser Gly Thr 1 5 <210> SEQ ID NO 183 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 183 Gly Leu Ala Thr Val Lys Ser 1 5 <210> SEQ ID NO 184 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 184 Gly Ala Thr Ser Phe Gly Leu 1 5 <210> SEQ ID NO 185 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 185 Lys Pro Pro Gly Pro Val Ser 1 5 <210> SEQ ID NO 186 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 186 Thr Leu Tyr Val Ser Gly Asn 1 5 <210> SEQ ID NO 187 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 187 His Ala Pro Phe Lys Ser Gln 1 5 <210> SEQ ID NO 188 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 188 Val Ala Phe Thr Arg Leu Pro 1 5 <210> SEQ ID NO 189 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 189 Leu Pro Thr Arg Thr Pro Ala 1 5 <210> SEQ ID NO 190 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 190 Ala Ser Phe Asp Leu Leu Ile 1 5 <210> SEQ ID NO 191 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 191 Arg Met Asn Thr Glu Pro Pro 1 5 <210> SEQ ID NO 192 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 192 Lys Met Thr Pro Leu Thr Thr 1 5 <210> SEQ ID NO 193 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 193 Ala Asn Ala Thr Pro Leu Leu 1 5 <210> SEQ ID NO 194 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 194 Thr Ile Trp Pro Pro Pro Val 1 5 <210> SEQ ID NO 195 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 195 Gln Thr Lys Val Met Thr Thr 1 5 <210> SEQ ID NO 196 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <400>SEQUENCE: 196 Asn His Ala Val Phe Ala Ser 1 5 <210> SEQ ID NO 197 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: m13 coliphage insert <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (5)...(5) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 197 Leu His Ala AlaXaa Thr Ser 1 5 <210> SEQ ID NO 198 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 198 Thr Trp Gln ProTyr Phe His 1 5 <210> SEQ ID NO 199 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 199 Ala Pro Leu AlaLeu His Ala 1 5 <210> SEQ ID NO 200 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 200 Thr Ala His AspLeu Thr Val 1 5 <210> SEQ ID NO 201 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 201 Asn Met Thr AsnMet Leu Thr 1 5 <210> SEQ ID NO 202 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 202 Gly Ser Gly LeuSer Gln Asp 1 5 <210> SEQ ID NO 203 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 203 Thr Pro Ile LysThr Ile Tyr 1 5 <210> SEQ ID NO 204 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 204 Ser His Leu TyrArg Ser Ser 1 5 <210> SEQ ID NO 205 <211> LENGTH: 7 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 205 His Gly Gln AlaTrp Gln Phe 1 5 <210> SEQ ID NO 206 <211> LENGTH: 4 <212> TYPE: PRT<213> ORGANISM: m13 coliphage insert <400> SEQUENCE: 206 Cys Gly Ser Gly1 <210> SEQ ID NO 207 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 207 Tyr Met Asp Gly Thr Met SerGln Val 1 5 <210> SEQ ID NO 208 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 208 His Trp Asp PheAla Trp Pro Trp Tyr Met Asp Gly Thr Met Ser Gln 1 5 10 15 Val <210> SEQID NO 209 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 209 Tyr Met Asp Gly Thr Met Ser Gln Val HisTrp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQ ID NO 210 <211> LENGTH:25 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 210 His Trp Asp Phe Ala Trp Pro Trp Tyr Met Asp Gly Thr MetSer Gln 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ IDNO 211 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 211 His Trp Asp Phe Ala Trp Pro Trp Tyr MetAsp Gly Thr Met Ser Gln 1 5 10 15 Val Trp Pro Trp Ala Phe Asp Trp His 2025 <210> SEQ ID NO 212 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 212 His Trp Asp Phe Ala Trp ProTrp Gly Ser Gly Tyr Met Asp Gly Thr 1 5 10 15 Met Ser Gln Val 20 <210>SEQ ID NO 213 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <400> SEQUENCE: 213 His Trp Asp Phe Ala Trp Pro TrpGly Ser Gly Tyr Met Asp Gly Thr 1 5 10 15 Met Ser Gln Val Gly Ser GlyTrp Pro Trp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 214 <211>LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 214 His Trp Asp PheAla Trp Pro Trp Xaa Xaa Xaa Tyr Met Asp Gly Thr 1 5 10 15 Met Ser GlnVal 20 <210> SEQ ID NO 215 <211> LENGTH: 20 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 215 Tyr Met Asp GlyThr Met Ser Gln Val Gly Ser Gly His Trp Asp Phe 1 5 10 15 Ala Trp ProTrp 20 <210> SEQ ID NO 216 <211> LENGTH: 31 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(21)...(23) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 216 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Tyr Met AspGly Thr 1 5 10 15 Met Ser Gln Val Xaa Xaa Xaa His Trp Asp Phe Ala TrpPro Trp 20 25 30 <210> SEQ ID NO 217 <211> LENGTH: 17 <212> TYPE: PRT<213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 217 His Trp AspPhe Ala Trp Pro Trp Tyr Met Asp Gly Thr Met Ser Gln 1 5 10 15 Val <210>SEQ ID NO 218 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <400> SEQUENCE: 218 Tyr Met Asp Gly Thr Met Ser GlnVal His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQ ID NO 219 <211>LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 219 His Trp Asp Phe Ala Trp Pro Trp Tyr Met Asp Gly Thr MetSer Gln 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ IDNO 220 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(10)...(12) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 220 Tyr Met Asp Gly Thr Met Ser Gln Val Xaa Xaa Xaa Trp ProTrp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 221 <211> LENGTH:31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 221 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Tyr Met Asp Gly Thr 1 5 10 15 Met Ser Gln Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 222 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:222 Tyr Met Asp Gly Thr Met Ser Gln Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 223 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 223 His Trp Asp PheAla Trp Pro Trp Tyr Met Asp Gly Thr Met Ser Gln 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 224 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 224 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Tyr Met Asn Gly Thr 1 5 10 15 Met Ser Gln Val 20 <210>SEQ ID NO 225 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 225 Tyr Met Asn Gly Thr Met Ser Gln Val Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 226 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 226 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Tyr Met Asn Gly Thr 1 5 10 15 Met Ser Gln Val Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 227 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:227 His Trp Asp Phe Ala Trp Pro Trp Tyr Met Asn Gly Thr Met Ser Gln 1 510 15 Val <210> SEQ ID NO 228 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 228 Tyr Met Asn GlyThr Met Ser Gln Val His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 229 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 229 His Trp Asp Phe Ala Trp Pro Trp Tyr MetAsn Gly Thr Met Ser Gln 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 230 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <221> NAME/KEY: VARIANT <222> LOCATION:(10)...(12) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 230 Tyr Met Asn Gly Thr Met Ser Gln Val Xaa Xaa Xaa Trp ProTrp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 231 <211> LENGTH:31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 231 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Tyr Met Asn Gly Thr 1 5 10 15 Met Ser Gln Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 232 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:232 Tyr Met Asn Gly Thr Met Ser Gln Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 233 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 233 His Trp Asp PheAla Trp Pro Trp Tyr Met Asn Gly Thr Met Ser Gln 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 234 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 234 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Met Leu Leu Ala Val 1 5 10 15 Leu Tyr Cys Leu 20 <210>SEQ ID NO 235 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 235 Met Leu Leu Ala Val Leu Tyr Cys Leu Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 236 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 236 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Met Leu Leu Ala Val 1 5 10 15 Leu Tyr Cys Leu Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 237 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:237 His Trp Asp Phe Ala Trp Pro Trp Met Leu Leu Ala Val Leu Tyr Cys 1 510 15 Leu <210> SEQ ID NO 238 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 238 Met Leu Leu AlaVal Leu Tyr Cys Leu His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 239 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 239 His Trp Asp Phe Ala Trp Pro Trp Met LeuLeu Ala Val Leu Tyr Cys 1 5 10 15 Leu His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 240 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 240 Met Leu Leu Ala Val Leu Tyr Cys Leu Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 241 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 241 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Met Leu Leu Ala Val 1 5 10 15 Leu Tyr Cys Leu Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 242 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:242 Met Leu Leu Ala Val Leu Tyr Cys Leu Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 243 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 243 His Trp Asp PheAla Trp Pro Trp Met Leu Leu Ala Val Leu Tyr Cys 1 5 10 15 Leu Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 244 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 244 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ile Met Asp Gln Val 1 5 10 15 Pro Phe Ser Val 20 <210>SEQ ID NO 245 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <400> SEQUENCE: 245 Ile Met Asp Gln Val Pro Phe SerVal Gly Ser Gly His Trp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQID NO 246 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(9)...(11) <223> OTHER INFORMATION: Any amino acid residue <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (21)...(23) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 246 His Trp Asp PheAla Trp Pro Trp Xaa Xaa Xaa Ile Met Asp Gln Val 1 5 10 15 Pro Phe SerVal Xaa Xaa Xaa His Trp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO247 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 247 His Trp Asp Phe Ala Trp Pro Trp Ile MetAsp Gln Val Pro Phe Ser 1 5 10 15 Val <210> SEQ ID NO 248 <211> LENGTH:17 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 248 Ile Met Asp Gln Val Pro Phe Ser Val His Trp Asp Phe AlaTrp Pro 1 5 10 15 Trp <210> SEQ ID NO 249 <211> LENGTH: 25 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 249 His TrpAsp Phe Ala Trp Pro Trp Ile Met Asp Gln Val Pro Phe Ser 1 5 10 15 ValHis Trp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 250 <211> LENGTH:20 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (10)...(12) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 250 Ile Met Asp GlnVal Pro Phe Ser Val Xaa Xaa Xaa Trp Pro Trp Ala 1 5 10 15 Phe Asp TrpHis 20 <210> SEQ ID NO 251 <211> LENGTH: 31 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(21)...(23) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 251 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Ile Met AspGln Val 1 5 10 15 Pro Phe Ser Val Xaa Xaa Xaa Trp Pro Trp Ala Phe AspTrp His 20 25 30 <210> SEQ ID NO 252 <211> LENGTH: 17 <212> TYPE: PRT<213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 252 Ile Met AspGln Val Pro Phe Ser Val Trp Pro Trp Ala Phe Asp Trp 1 5 10 15 His <210>SEQ ID NO 253 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <400> SEQUENCE: 253 His Trp Asp Phe Ala Trp Pro TrpIle Met Asp Gln Val Pro Phe Ser 1 5 10 15 Val Trp Pro Trp Ala Phe AspTrp His 20 25 <210> SEQ ID NO 254 <211> LENGTH: 20 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <400> SEQUENCE: 254 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa XaaIle Thr Asp Gln Val 1 5 10 15 Pro Phe Ser Val 20 <210> SEQ ID NO 255<211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative<220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (10)...(12) <223>OTHER INFORMATION: Any amino acid residue <400> SEQUENCE: 255 Ile ThrAsp Gln Val Pro Phe Ser Val Xaa Xaa Xaa His Trp Asp Phe 1 5 10 15 AlaTrp Pro Trp 20 <210> SEQ ID NO 256 <211> LENGTH: 31 <212> TYPE: PRT<213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any aminoacid residue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(21)...(23) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 256 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Ile Thr AspGln Val 1 5 10 15 Pro Phe Ser Val Xaa Xaa Xaa His Trp Asp Phe Ala TrpPro Trp 20 25 30 <210> SEQ ID NO 257 <211> LENGTH: 17 <212> TYPE: PRT<213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 257 His Trp AspPhe Ala Trp Pro Trp Ile Thr Asp Gln Val Pro Phe Ser 1 5 10 15 Val <210>SEQ ID NO 258 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <400> SEQUENCE: 258 Ile Thr Asp Gln Val Pro Phe SerVal His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQ ID NO 259 <211>LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 259 His Trp Asp Phe Ala Trp Pro Trp Ile Thr Asp Gln Val ProPhe Ser 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ IDNO 260 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(10)...(12) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 260 Ile Thr Asp Gln Val Pro Phe Ser Val Xaa Xaa Xaa Trp ProTrp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 261 <211> LENGTH:31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 261 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ile Thr Asp Gln Val 1 5 10 15 Pro Phe Ser Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 262 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:262 Ile Thr Asp Gln Val Pro Phe Ser Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 263 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 263 His Trp Asp PheAla Trp Pro Trp Ile Thr Asp Gln Val Pro Phe Ser 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 264 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 264 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Thr Ile Thr Asp Gln 1 5 10 15 Val Pro Phe Ser Val 20<210> SEQ ID NO 265 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 265 Thr Ile Thr Asp Gln Val Pro Phe Ser Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 266 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 266 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Thr Ile Thr Asp Gln 1 5 10 15 Val Pro Phe Ser Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 267 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 267 His Trp Asp Phe Ala Trp Pro Trp Thr Ile Thr Asp Gln ValPro Phe 1 5 10 15 Ser Val <210> SEQ ID NO 268 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 268Thr Ile Thr Asp Gln Val Pro Phe Ser Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 269 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 269 His Trp Asp PheAla Trp Pro Trp Thr Ile Thr Asp Gln Val Pro Phe 1 5 10 15 Ser Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 270 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 270 Thr Ile Thr AspGln Val Pro Phe Ser Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 271 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 271 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Thr Ile ThrAsp Gln 1 5 10 15 Val Pro Phe Ser Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 272 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 272 Thr IleThr Asp Gln Val Pro Phe Ser Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 273 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 273 His Trp Asp Phe Ala Trp ProTrp Thr Ile Thr Asp Gln Val Pro Phe 1 5 10 15 Ser Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 274 <211> LENGTH: 19 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 274 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Tyr Leu Glu Pro Gly 1 5 10 15 Val Thr Val <210> SEQ IDNO 275 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(9)...(11) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 275 Tyr Leu Glu Pro Gly Val Thr Val Xaa Xaa Xaa His Trp AspPhe Ala 1 5 10 15 Trp Pro Trp <210> SEQ ID NO 276 <211> LENGTH: 30 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (20)...(22) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 276 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Tyr LeuGlu Pro Gly 1 5 10 15 Val Thr Val Xaa Xaa Xaa His Trp Asp Phe Ala TrpPro Trp 20 25 30 <210> SEQ ID NO 277 <211> LENGTH: 16 <212> TYPE: PRT<213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 277 His Trp AspPhe Ala Trp Pro Trp Tyr Leu Glu Pro Gly Val Thr Val 1 5 10 15 <210> SEQID NO 278 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 278 Tyr Leu Glu Pro Gly Val Thr Val His TrpAsp Phe Ala Trp Pro Trp 1 5 10 15 <210> SEQ ID NO 279 <211> LENGTH: 24<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:279 His Trp Asp Phe Ala Trp Pro Trp Tyr Leu Glu Pro Gly Val Thr Val 1 510 15 His Trp Asp Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 280 <211>LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 280 Tyr Leu Glu ProGly Val Thr Val Xaa Xaa Xaa Trp Pro Trp Ala Phe 1 5 10 15 Asp Trp His<210> SEQ ID NO 281 <211> LENGTH: 30 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acid residue<220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (20)...(22) <223>OTHER INFORMATION: Any amino acid residue <400> SEQUENCE: 281 His TrpAsp Phe Ala Trp Pro Trp Xaa Xaa Xaa Tyr Leu Glu Pro Gly 1 5 10 15 ValThr Val Xaa Xaa Xaa Trp Pro Trp Ala Phe Asp Trp His 20 25 30 <210> SEQID NO 282 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 282 Tyr Leu Glu Pro Gly Val Thr Val Trp ProTrp Ala Phe Asp Trp His 1 5 10 15 <210> SEQ ID NO 283 <211> LENGTH: 24<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:283 His Trp Asp Phe Ala Trp Pro Trp Tyr Leu Glu Pro Gly Val Thr Val 1 510 15 Trp Pro Trp Ala Phe Asp Trp His 20 <210> SEQ ID NO 284 <211>LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 284 His Trp Asp PheAla Trp Pro Trp Xaa Xaa Xaa Tyr Leu Glu Pro Gly 1 5 10 15 Val Thr ValAla 20 <210> SEQ ID NO 285 <211> LENGTH: 20 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acidresidue <400> SEQUENCE: 285 Tyr Leu Glu Pro Gly Val Thr Val Ala Xaa XaaXaa His Trp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 286<211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative<220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223>OTHER INFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 286 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Tyr Leu Glu Pro Gly 1 5 10 15 Val Thr Val Ala Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 287 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:287 His Trp Asp Phe Ala Trp Pro Trp Tyr Leu Glu Pro Gly Val Thr Val 1 510 15 Ala <210> SEQ ID NO 288 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 288 Tyr Leu Glu ProGly Val Thr Val Ala His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 289 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 289 His Trp Asp Phe Ala Trp Pro Trp Tyr LeuGlu Pro Gly Val Thr Val 1 5 10 15 Ala His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 290 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 290 Tyr Leu Glu Pro Gly Val Thr Val Ala Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 291 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 291 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Tyr Leu Glu Pro Gly 1 5 10 15 Val Thr Val Ala Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 292 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:292 Tyr Leu Glu Pro Gly Val Thr Val Ala Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 293 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 293 His Trp Asp PheAla Trp Pro Trp Tyr Leu Glu Pro Gly Val Thr Val 1 5 10 15 Ala Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 294 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 294 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Lys Thr Trp Gly Gln 1 5 10 15 Tyr Trp Gln Val 20 <210>SEQ ID NO 295 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 295 Lys Thr Trp Gly Gln Tyr Trp Gln Val Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 296 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 296 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Lys Thr Trp Gly Gln 1 5 10 15 Tyr Trp Gln Val Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 297 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:297 His Trp Asp Phe Ala Trp Pro Trp Lys Thr Trp Gly Gln Tyr Trp Gln 1 510 15 Val <210> SEQ ID NO 298 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 298 Lys Thr Trp GlyGln Tyr Trp Gln Val His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 299 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 299 His Trp Asp Phe Ala Trp Pro Trp Lys ThrTrp Gly Gln Tyr Trp Gln 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 300 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 300 Lys Thr Trp Gly Gln Tyr Trp Gln Val Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 301 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 301 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Lys Thr Trp Gly Gln 1 5 10 15 Tyr Trp Gln Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 302 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:302 Lys Thr Trp Gly Gln Tyr Trp Gln Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 303 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 303 His Trp Asp PheAla Trp Pro Trp Lys Thr Trp Gly Gln Tyr Trp Gln 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 304 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 304 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Lys Thr Trp Gly Gln 1 5 10 15 Tyr Trp Gln Val Leu 20<210> SEQ ID NO 305 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 305 Lys Thr Trp Gly Gln Tyr Trp Gln Val Leu Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 306 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 306 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Lys Thr Trp Gly Gln 1 5 10 15 Tyr Trp Gln Val Leu Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 307 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 307 His Trp Asp Phe Ala Trp Pro Trp Lys Thr Trp Gly Gln TyrTrp Gln 1 5 10 15 Val Leu <210> SEQ ID NO 308 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 308Lys Thr Trp Gly Gln Tyr Trp Gln Val Leu His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 309 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 309 His Trp Asp PheAla Trp Pro Trp Lys Thr Trp Gly Gln Tyr Trp Gln 1 5 10 15 Val Leu HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 310 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 310 Lys Thr Trp GlyGln Tyr Trp Gln Val Leu Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 311 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 311 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Lys Thr TrpGly Gln 1 5 10 15 Tyr Trp Gln Val Leu Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 312 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 312 Lys ThrTrp Gly Gln Tyr Trp Gln Val Leu Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 313 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 313 His Trp Asp Phe Ala Trp ProTrp Lys Thr Trp Gly Gln Tyr Trp Gln 1 5 10 15 Val Leu Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 314 <211> LENGTH: 20 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 314 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Val Leu Lys Arg Cys 1 5 10 15 Leu Leu His Leu 20 <210>SEQ ID NO 315 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 315 Val Leu Lys Arg Cys Leu Leu His Leu Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 316 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 316 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Val Leu Lys Arg Cys 1 5 10 15 Leu Leu His Leu Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 317 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:317 His Trp Asp Phe Ala Trp Pro Trp Val Leu Lys Arg Cys Leu Leu His 1 510 15 Leu <210> SEQ ID NO 318 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 318 Val Leu Lys ArgCys Leu Leu His Leu His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 319 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 319 His Trp Asp Phe Ala Trp Pro Trp Val LeuLys Arg Cys Leu Leu His 1 5 10 15 Leu His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 320 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 320 Val Leu Lys Arg Cys Leu Leu His Leu Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 321 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 321 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Val Leu Lys Arg Cys 1 5 10 15 Leu Leu His Leu Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 322 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:322 Val Leu Lys Arg Cys Leu Leu His Leu Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 323 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 323 His Trp Asp PheAla Trp Pro Trp Val Leu Lys Arg Cys Leu Leu His 1 5 10 15 Leu Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 324 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 324 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Leu Asn Val Ser Leu 1 5 10 15 Ala Asp Thr Asn 20 <210>SEQ ID NO 325 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 325 Leu Asn Val Ser Leu Ala Asp Thr Asn Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 326 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 326 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Leu Asn Val Ser Leu 1 5 10 15 Ala Asp Thr Asn Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 327 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:327 His Trp Asp Phe Ala Trp Pro Trp Leu Asn Val Ser Leu Ala Asp Thr 1 510 15 Asn <210> SEQ ID NO 328 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 328 Leu Asn Val SerLeu Ala Asp Thr Asn His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 329 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 329 His Trp Asp Phe Ala Trp Pro Trp Leu AsnVal Ser Leu Ala Asp Thr 1 5 10 15 Asn His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 330 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 330 Leu Asn Val Ser Leu Ala Asp Thr Asn Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 331 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 331 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Leu Asn Val Ser Leu 1 5 10 15 Ala Asp Thr Asn Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 332 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:332 Leu Asn Val Ser Leu Ala Asp Thr Asn Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 333 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 333 His Trp Asp PheAla Trp Pro Trp Leu Asn Val Ser Leu Ala Asp Thr 1 5 10 15 Asn Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 334 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 334 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ser Leu Ala Asp Thr 1 5 10 15 Asn Ser Leu Ala Val 20<210> SEQ ID NO 335 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 335 Ser Leu Ala Asp Thr Asn Ser Leu Ala Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 336 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 336 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ser Leu Ala Asp Thr 1 5 10 15 Asn Ser Leu Ala Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 337 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 337 His Trp Asp Phe Ala Trp Pro Trp Ser Leu Ala Asp Thr AsnSer Leu 1 5 10 15 Ala Val <210> SEQ ID NO 338 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 338Ser Leu Ala Asp Thr Asn Ser Leu Ala Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 339 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 339 His Trp Asp PheAla Trp Pro Trp Ser Leu Ala Asp Thr Asn Ser Leu 1 5 10 15 Ala Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 340 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 340 Ser Leu Ala AspThr Asn Ser Leu Ala Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 341 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 341 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Ser Leu AlaAsp Thr 1 5 10 15 Asn Ser Leu Ala Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 342 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 342 Ser LeuAla Asp Thr Asn Ser Leu Ala Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 343 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 343 His Trp Asp Phe Ala Trp ProTrp Ser Leu Ala Asp Thr Asn Ser Leu 1 5 10 15 Ala Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 344 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 344 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Leu Leu Asp Gly Thr 1 5 10 15 Ala Thr Leu Arg Leu 20<210> SEQ ID NO 345 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 345 Leu Leu Asp Gly Thr Ala Thr Leu Arg Leu Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 346 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 346 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Leu Leu Asp Gly Thr 1 5 10 15 Ala Thr Leu Arg Leu Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 347 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 347 His Trp Asp Phe Ala Trp Pro Trp Leu Leu Asp Gly Thr AlaThr Leu 1 5 10 15 Arg Leu <210> SEQ ID NO 348 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 348Leu Leu Asp Gly Thr Ala Thr Leu Arg Leu His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 349 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 349 His Trp Asp PheAla Trp Pro Trp Leu Leu Asp Gly Thr Ala Thr Leu 1 5 10 15 Arg Leu HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 350 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 350 Leu Leu Asp GlyThr Ala Thr Leu Arg Leu Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 351 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 351 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Leu Leu AspGly Thr 1 5 10 15 Ala Thr Leu Arg Leu Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 352 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 352 Leu LeuAsp Gly Thr Ala Thr Leu Arg Leu Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 353 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 353 His Trp Asp Phe Ala Trp ProTrp Leu Leu Asp Gly Thr Ala Thr Leu 1 5 10 15 Arg Leu Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 354 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 354 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Val Leu Tyr Arg Tyr 1 5 10 15 Gly Ser Phe Ser Val 20<210> SEQ ID NO 355 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 355 Val Leu Tyr Arg Tyr Gly Ser Phe Ser Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 356 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 356 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Val Leu Tyr Arg Tyr 1 5 10 15 Gly Ser Phe Ser Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 357 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 357 His Trp Asp Phe Ala Trp Pro Trp Val Leu Tyr Arg Tyr GlySer Phe 1 5 10 15 Ser Val <210> SEQ ID NO 358 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 358Val Leu Tyr Arg Tyr Gly Ser Phe Ser Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 359 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 359 His Trp Asp PheAla Trp Pro Trp Val Leu Tyr Arg Tyr Gly Ser Phe 1 5 10 15 Ser Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 360 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 360 Val Leu Tyr ArgTyr Gly Ser Phe Ser Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 361 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 361 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Val Leu TyrArg Tyr 1 5 10 15 Gly Ser Phe Ser Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 362 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 362 Val LeuTyr Arg Tyr Gly Ser Phe Ser Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 363 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 363 His Trp Asp Phe Ala Trp ProTrp Val Leu Tyr Arg Tyr Gly Ser Phe 1 5 10 15 Ser Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 364 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 364 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ala Leu Asp Gly Gly 1 5 10 15 Asn Lys His Phe Leu 20<210> SEQ ID NO 365 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 365 Ala Leu Asp Gly Gly Asn Lys His Phe Leu Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 366 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 366 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ala Leu Asp Gly Gly 1 5 10 15 Asn Lys His Phe Leu Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 367 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 367 His Trp Asp Phe Ala Trp Pro Trp Ala Leu Asp Gly Gly AsnLys His 1 5 10 15 Phe Leu <210> SEQ ID NO 368 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 368Ala Leu Asp Gly Gly Asn Lys His Phe Leu His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 369 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 369 His Trp Asp PheAla Trp Pro Trp Ala Leu Asp Gly Gly Asn Lys His 1 5 10 15 Phe Leu HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 370 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 370 Ala Leu Asp GlyGly Asn Lys His Phe Leu Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 371 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 371 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Ala Leu AspGly Gly 1 5 10 15 Asn Lys His Phe Leu Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 372 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 372 Ala LeuAsp Gly Gly Asn Lys His Phe Leu Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 373 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 373 His Trp Asp Phe Ala Trp ProTrp Ala Leu Asp Gly Gly Asn Lys His 1 5 10 15 Phe Leu Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 374 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 374 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Val Leu Pro Ser Pro 1 5 10 15 Ala Cys Gln Leu Val 20<210> SEQ ID NO 375 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 375 Val Leu Pro Ser Pro Ala Cys Gln Leu Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 376 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 376 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Val Leu Pro Ser Pro 1 5 10 15 Ala Cys Gln Leu Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 377 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 377 His Trp Asp Phe Ala Trp Pro Trp Val Leu Pro Ser Pro AlaCys Gln 1 5 10 15 Leu Val <210> SEQ ID NO 378 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 378Val Leu Pro Ser Pro Ala Cys Gln Leu Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 379 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 379 His Trp Asp PheAla Trp Pro Trp Val Leu Pro Ser Pro Ala Cys Gln 1 5 10 15 Leu Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 380 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 380 Val Leu Pro SerPro Ala Cys Gln Leu Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 381 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 381 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Val Leu ProSer Pro 1 5 10 15 Ala Cys Gln Leu Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 382 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 382 Val LeuPro Ser Pro Ala Cys Gln Leu Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 383 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 383 His Trp Asp Phe Ala Trp ProTrp Val Leu Pro Ser Pro Ala Cys Gln 1 5 10 15 Leu Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 384 <211> LENGTH: 20 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 384 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ala Ala Gly Ile Gly 1 5 10 15 Ile Leu Thr Val 20 <210>SEQ ID NO 385 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 385 Ala Ala Gly Ile Gly Ile Leu Thr Val Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 386 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 386 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ala Ala Gly Ile Gly 1 5 10 15 Ile Leu Thr Val Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 387 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:387 His Trp Asp Phe Ala Trp Pro Trp Ala Ala Gly Ile Gly Ile Leu Thr 1 510 15 Val <210> SEQ ID NO 388 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 388 Ala Ala Gly IleGly Ile Leu Thr Val His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 389 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 389 His Trp Asp Phe Ala Trp Pro Trp Ala AlaGly Ile Gly Ile Leu Thr 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 390 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 390 Ala Ala Gly Ile Gly Ile Leu Thr Val Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 391 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 391 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ala Ala Gly Ile Gly 1 5 10 15 Ile Leu Thr Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 392 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:392 Ala Ala Gly Ile Gly Ile Leu Thr Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 393 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 393 His Trp Asp PheAla Trp Pro Trp Ala Ala Gly Ile Gly Ile Leu Thr 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 394 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 394 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Glu Ala Ala Gly Ile 1 5 10 15 Gly Ile Leu Thr Val 20<210> SEQ ID NO 395 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 395 Glu Ala Ala Gly Ile Gly Ile Leu Thr Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 396 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 396 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Glu Ala Ala Gly Ile 1 5 10 15 Gly Ile Leu Thr Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 397 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 397 His Trp Asp Phe Ala Trp Pro Trp Glu Ala Ala Gly Ile GlyIle Leu 1 5 10 15 Thr Val <210> SEQ ID NO 398 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 398Glu Ala Ala Gly Ile Gly Ile Leu Thr Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 399 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 399 His Trp Asp PheAla Trp Pro Trp Glu Ala Ala Gly Ile Gly Ile Leu 1 5 10 15 Thr Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 400 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 400 Glu Ala Ala GlyIle Gly Ile Leu Thr Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 401 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 401 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Glu Ala AlaGly Ile 1 5 10 15 Gly Ile Leu Thr Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 402 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 402 Glu AlaAla Gly Ile Gly Ile Leu Thr Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 403 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 403 His Trp Asp Phe Ala Trp ProTrp Glu Ala Ala Gly Ile Gly Ile Leu 1 5 10 15 Thr Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 404 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 404 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Glu Ala Ala Gly Gly 1 5 10 15 Ile Leu Thr Val Ile 20<210> SEQ ID NO 405 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 405 Glu Ala Ala Gly Gly Ile Leu Thr Val Ile Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 406 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 406 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Glu Ala Ala Gly Gly 1 5 10 15 Ile Leu Thr Val Ile Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 407 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 407 His Trp Asp Phe Ala Trp Pro Trp Glu Ala Ala Gly Gly IleLeu Thr 1 5 10 15 Val Ile <210> SEQ ID NO 408 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 408Glu Ala Ala Gly Gly Ile Leu Thr Val Ile His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 409 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 409 His Trp Asp PheAla Trp Pro Trp Glu Ala Ala Gly Gly Ile Leu Thr 1 5 10 15 Val Ile HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 410 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 410 Glu Ala Ala GlyGly Ile Leu Thr Val Ile Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 411 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 411 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Glu Ala AlaGly Gly 1 5 10 15 Ile Leu Thr Val Ile Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 412 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 412 Glu AlaAla Gly Gly Ile Leu Thr Val Ile Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 413 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 413 His Trp Asp Phe Ala Trp ProTrp Glu Ala Ala Gly Gly Ile Leu Thr 1 5 10 15 Val Ile Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 414 <211> LENGTH: 20 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 414 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ile Leu Thr Val Ile 1 5 10 15 Leu Gly Val Leu 20 <210>SEQ ID NO 415 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 415 Ile Leu Thr Val Ile Leu Gly Val Leu Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 416 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 416 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ile Leu Thr Val Ile 1 5 10 15 Leu Gly Val Leu Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 417 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:417 His Trp Asp Phe Ala Trp Pro Trp Ile Leu Thr Val Ile Leu Gly Val 1 510 15 Leu <210> SEQ ID NO 418 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 418 Ile Leu Thr ValIle Leu Gly Val Leu His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 419 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 419 His Trp Asp Phe Ala Trp Pro Trp Ile LeuThr Val Ile Leu Gly Val 1 5 10 15 Leu His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 420 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 420 Ile Leu Thr Val Ile Leu Gly Val Leu Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 421 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 421 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ile Leu Thr Val Ile 1 5 10 15 Leu Gly Val Leu Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 422 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:422 Ile Leu Thr Val Ile Leu Gly Val Leu Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 423 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 423 His Trp Asp PheAla Trp Pro Trp Ile Leu Thr Val Ile Leu Gly Val 1 5 10 15 Leu Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 424 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 424 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ala Leu Glu Ala Gln 1 5 10 15 Gln Glu Ala Leu 20 <210>SEQ ID NO 425 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 425 Ala Leu Glu Ala Gln Gln Glu Ala Leu Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 426 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 426 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ala Leu Glu Ala Gln 1 5 10 15 Gln Glu Ala Leu Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 427 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:427 His Trp Asp Phe Ala Trp Pro Trp Ala Leu Glu Ala Gln Gln Glu Ala 1 510 15 Leu <210> SEQ ID NO 428 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 428 Ala Leu Glu AlaGln Gln Glu Ala Leu His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 429 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 429 His Trp Asp Phe Ala Trp Pro Trp Ala LeuGlu Ala Gln Gln Glu Ala 1 5 10 15 Leu His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 430 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 430 Ala Leu Glu Ala Gln Gln Glu Ala Leu Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 431 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 431 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ala Leu Glu Ala Gln 1 5 10 15 Gln Glu Ala Leu Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 432 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:432 Ala Leu Glu Ala Gln Gln Glu Ala Leu Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 433 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 433 His Trp Asp PheAla Trp Pro Trp Ala Leu Glu Ala Gln Gln Glu Ala 1 5 10 15 Leu Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 434 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 434 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ile Leu Glu Ser Leu 1 5 10 15 Phe Arg Ala Val 20 <210>SEQ ID NO 435 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 435 Ile Leu Glu Ser Leu Phe Arg Ala Val Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 436 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 436 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ile Leu Glu Ser Leu 1 5 10 15 Phe Arg Ala Val Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 437 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:437 His Trp Asp Phe Ala Trp Pro Trp Ile Leu Glu Ser Leu Phe Arg Ala 1 510 15 Val <210> SEQ ID NO 438 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 438 Ile Leu Glu SerLeu Phe Arg Ala Val His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 439 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 439 His Trp Asp Phe Ala Trp Pro Trp Ile LeuGlu Ser Leu Phe Arg Ala 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 440 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 440 Ile Leu Glu Ser Leu Phe Arg Ala Val Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 441 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 441 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ile Leu Glu Ser Leu 1 5 10 15 Phe Arg Ala Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 442 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:442 Ile Leu Glu Ser Leu Phe Arg Ala Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 443 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 443 His Trp Asp PheAla Trp Pro Trp Ile Leu Glu Ser Leu Phe Arg Ala 1 5 10 15 Val Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 444 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 444 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Ser Leu His Cys Lys 1 5 10 15 Pro Glu Glu Ala Leu 20<210> SEQ ID NO 445 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 445 Ser Leu His Cys Lys Pro Glu Glu Ala Leu Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 446 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 446 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Ser Leu His Cys Lys 1 5 10 15 Pro Glu Glu Ala Leu Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 447 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 447 His Trp Asp Phe Ala Trp Pro Trp Ser Leu His Cys Lys ProGlu Glu 1 5 10 15 Ala Leu <210> SEQ ID NO 448 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 448Ser Leu His Cys Lys Pro Glu Glu Ala Leu His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 449 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 449 His Trp Asp PheAla Trp Pro Trp Ser Leu His Cys Lys Pro Glu Glu 1 5 10 15 Ala Leu HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 450 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 450 Ser Leu His CysLys Pro Glu Glu Ala Leu Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 451 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 451 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Ser Leu HisCys Lys 1 5 10 15 Pro Glu Glu Ala Leu Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 452 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 452 Ser LeuHis Cys Lys Pro Glu Glu Ala Leu Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 453 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 453 His Trp Asp Phe Ala Trp ProTrp Ser Leu His Cys Lys Pro Glu Glu 1 5 10 15 Ala Leu Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 454 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 454 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Pro Leu Val Leu Gly 1 5 10 15 Thr Leu Glu Glu Val 20<210> SEQ ID NO 455 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 455 Pro Leu Val Leu Gly Thr Leu Glu Glu Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 456 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 456 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Pro Leu Val Leu Gly 1 5 10 15 Thr Leu Glu Glu Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 457 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 457 His Trp Asp Phe Ala Trp Pro Trp Pro Leu Val Leu Gly ThrLeu Glu 1 5 10 15 Glu Val <210> SEQ ID NO 458 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 458Pro Leu Val Leu Gly Thr Leu Glu Glu Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 459 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 459 His Trp Asp PheAla Trp Pro Trp Pro Leu Val Leu Gly Thr Leu Glu 1 5 10 15 Glu Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 460 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 460 Pro Leu Val LeuGly Thr Leu Glu Glu Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 461 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 461 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Pro Leu ValLeu Gly 1 5 10 15 Thr Leu Glu Glu Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 462 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 462 Pro LeuVal Leu Gly Thr Leu Glu Glu Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 463 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 463 His Trp Asp Phe Ala Trp ProTrp Ile Pro Leu Val Leu Gly Thr Leu 1 5 10 15 Glu Glu Val Trp Pro TrpAla Phe Asp Trp His 20 25 <210> SEQ ID NO 464 <211> LENGTH: 20 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 464 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Cys Leu Gly Leu Ser 1 5 10 15 Tyr Asp Gly Leu 20 <210>SEQ ID NO 465 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 465 Cys Leu Gly Leu Ser Tyr Asp Gly Leu Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 466 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 466 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Cys Leu Gly Leu Ser 1 5 10 15 Tyr Asp Gly Leu Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 467 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:467 His Trp Asp Phe Ala Trp Pro Trp Cys Leu Gly Leu Ser Tyr Asp Gly 1 510 15 Leu <210> SEQ ID NO 468 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 468 Cys Leu Gly LeuSer Tyr Asp Gly Leu His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 469 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 469 His Trp Asp Phe Ala Trp Pro Trp Cys LeuGly Leu Ser Tyr Asp Gly 1 5 10 15 Leu His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 470 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 470 Cys Leu Gly Leu Ser Tyr Asp Gly Leu Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 471 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 471 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Cys Leu Gly Leu Ser 1 5 10 15 Tyr Asp Gly Leu Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 472 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:472 Cys Leu Gly Leu Ser Tyr Asp Gly Leu Trp Pro Trp Ala Phe Asp Trp 1 510 15 His <210> SEQ ID NO 473 <211> LENGTH: 25 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 473 His Trp Asp PheAla Trp Pro Trp Cys Leu Gly Leu Ser Tyr Asp Gly 1 5 10 15 Leu Trp ProTrp Ala Phe Asp Trp His 20 25 <210> SEQ ID NO 474 <211> LENGTH: 21 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 474 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Cys Leu Gly Leu Ser 1 5 10 15 Tyr Asp Gly Leu Leu 20<210> SEQ ID NO 475 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 475 Cys Leu Gly Leu Ser Tyr Asp Gly Leu Leu Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 476 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 476 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Cys Leu Gly Leu Ser 1 5 10 15 Tyr Asp Gly Leu Leu Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 477 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 477 His Trp Asp Phe Ala Trp Pro Trp Cys Leu Gly Leu Ser TyrAsp Gly 1 5 10 15 Leu Leu <210> SEQ ID NO 478 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 478Cys Leu Gly Leu Ser Tyr Asp Gly Leu Leu His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 479 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 479 His Trp Asp PheAla Trp Pro Trp Cys Leu Gly Leu Ser Tyr Asp Gly 1 5 10 15 Leu Leu HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 480 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 480 Cys Leu Gly LeuSer Tyr Asp Gly Leu Leu Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 481 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 481 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Cys Leu GlyLeu Ser 1 5 10 15 Tyr Asp Gly Leu Leu Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 482 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 482 Cys LeuGly Leu Ser Tyr Asp Gly Leu Leu Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 483 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 483 His Trp Asp Phe Ala Trp ProTrp Cys Leu Gly Leu Ser Tyr Asp Gly 1 5 10 15 Leu Leu Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 484 <211> LENGTH: 21 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 484 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Leu Leu Lys Tyr Arg 1 5 10 15 Ala Arg Glu Pro Val 20<210> SEQ ID NO 485 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (11)...(13) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 485 Leu Leu Lys Tyr Arg Ala Arg Glu Pro Val Xaa Xaa XaaHis Trp Asp 1 5 10 15 Phe Ala Trp Pro Trp 20 <210> SEQ ID NO 486 <211>LENGTH: 32 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (22)...(24) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 486 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Leu Leu Lys Tyr Arg 1 5 10 15 Ala Arg Glu Pro Val Xaa Xaa Xaa HisTrp Asp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 487 <211> LENGTH:18 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400>SEQUENCE: 487 His Trp Asp Phe Ala Trp Pro Trp Leu Leu Lys Tyr Arg AlaArg Glu 1 5 10 15 Pro Val <210> SEQ ID NO 488 <211> LENGTH: 18 <212>TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 488Leu Leu Lys Tyr Arg Ala Arg Glu Pro Val His Trp Asp Phe Ala Trp 1 5 1015 Pro Trp <210> SEQ ID NO 489 <211> LENGTH: 26 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 489 His Trp Asp PheAla Trp Pro Trp Leu Leu Lys Tyr Arg Ala Arg Glu 1 5 10 15 Pro Val HisTrp Asp Phe Ala Trp Pro Trp 20 25 <210> SEQ ID NO 490 <211> LENGTH: 21<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE:<221> NAME/KEY: VARIANT <222> LOCATION: (11)...(13) <223> OTHERINFORMATION: Any amino acid residue <400> SEQUENCE: 490 Leu Leu Lys TyrArg Ala Arg Glu Pro Val Xaa Xaa Xaa Trp Pro Trp 1 5 10 15 Ala Phe AspTrp His 20 <210> SEQ ID NO 491 <211> LENGTH: 32 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT<222> LOCATION: (9)...(11) <223> OTHER INFORMATION: Any amino acidresidue <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION:(22)...(24) <223> OTHER INFORMATION: Any amino acid residue <400>SEQUENCE: 491 His Trp Asp Phe Ala Trp Pro Trp Xaa Xaa Xaa Leu Leu LysTyr Arg 1 5 10 15 Ala Arg Glu Pro Val Xaa Xaa Xaa Trp Pro Trp Ala PheAsp Trp His 20 25 30 <210> SEQ ID NO 492 <211> LENGTH: 18 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE: 492 Leu LeuLys Tyr Arg Ala Arg Glu Pro Val Trp Pro Trp Ala Phe Asp 1 5 10 15 TrpHis <210> SEQ ID NO 493 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <400> SEQUENCE: 493 His Trp Asp Phe Ala Trp ProTrp Leu Leu Lys Tyr Arg Ala Arg Glu 1 5 10 15 Pro Val Trp Pro Trp AlaPhe Asp Trp His 20 25 <210> SEQ ID NO 494 <211> LENGTH: 20 <212> TYPE:PRT <213> ORGANISM: Homo sapiens derivative <220> FEATURE: <221>NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHER INFORMATION:Any amino acid residue <400> SEQUENCE: 494 His Trp Asp Phe Ala Trp ProTrp Xaa Xaa Xaa Phe Leu Trp Gly Pro 1 5 10 15 Arg Ala Leu Val 20 <210>SEQ ID NO 495 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Homosapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 495 Phe Leu Trp Gly Pro Arg Ala Leu Val Xaa Xaa Xaa HisTrp Asp Phe 1 5 10 15 Ala Trp Pro Trp 20 <210> SEQ ID NO 496 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 496 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Phe Leu Trp Gly Pro 1 5 10 15 Arg Ala Leu Val Xaa Xaa Xaa His TrpAsp Phe Ala Trp Pro Trp 20 25 30 <210> SEQ ID NO 497 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:497 His Trp Asp Phe Ala Trp Pro Trp Phe Leu Trp Gly Pro Arg Ala Leu 1 510 15 Val <210> SEQ ID NO 498 <211> LENGTH: 17 <212> TYPE: PRT <213>ORGANISM: Homo sapiens derivative <400> SEQUENCE: 498 Phe Leu Trp GlyPro Arg Ala Leu Val His Trp Asp Phe Ala Trp Pro 1 5 10 15 Trp <210> SEQID NO 499 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiensderivative <400> SEQUENCE: 499 His Trp Asp Phe Ala Trp Pro Trp Phe LeuTrp Gly Pro Arg Ala Leu 1 5 10 15 Val His Trp Asp Phe Ala Trp Pro Trp 2025 <210> SEQ ID NO 500 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM:Homo sapiens derivative <220> FEATURE: <221> NAME/KEY: VARIANT <222>LOCATION: (10)...(12) <223> OTHER INFORMATION: Any amino acid residue<400> SEQUENCE: 500 Phe Leu Trp Gly Pro Arg Ala Leu Val Xaa Xaa Xaa TrpPro Trp Ala 1 5 10 15 Phe Asp Trp His 20 <210> SEQ ID NO 501 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <220>FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: (9)...(11) <223> OTHERINFORMATION: Any amino acid residue <220> FEATURE: <221> NAME/KEY:VARIANT <222> LOCATION: (21)...(23) <223> OTHER INFORMATION: Any aminoacid residue <400> SEQUENCE: 501 His Trp Asp Phe Ala Trp Pro Trp Xaa XaaXaa Phe Leu Trp Gly Pro 1 5 10 15 Arg Ala Leu Val Xaa Xaa Xaa Trp ProTrp Ala Phe Asp Trp His 20 25 30 <210> SEQ ID NO 502 <211> LENGTH: 17<212> TYPE: PRT <213> ORGANISM: Homo sapiens derivative <400> SEQUENCE:502 Phe Leu Trp Gly Pro Arg Ala Leu Val Trp Pro Trp Ala Phe Asp Trp 1 510 15 His

We claim:
 1. A method of inducing an immune response in a subjectcomprising administering to said subject a therapeutic amount of animmunotherapeutic composition comprising a heat shock protein and amelanoma antigen, wherein the melanoma antigen is selected from thegroup consisting of tyrosinase, tyrosinase related protein 1, tyrosinaserelated protein 2, gp100, MAGE antigens, BAGE antigens, NYES01, MARTantigens, GM2, antigenic portions thereof and combinations thereof,wherein the melanoma antigen is covalently bound to a javelin molecule,and wherein the melanoma antigen bound to the javelin molecule isnon-covalently bound to the heat shock protein.
 2. The method of claim 1wherein the melanoma antigen is a peptide selected from the groupconsisting of peptides having sequencesTyr-Met-Asp-Gly-Thr-Met-Ser-Gln-Val (SEQ ID NO: ),Tyr-Met-Asn-Gly-Thr-Met-Ser-Gln-Val (SEQ ID NO: ),Met-Leu-Leu-Ala-Val-Leu-Tyr-Val-Leu (SEQ ID NO: ),Met-Ser-Leu-Gln-Arg-Gln-Phe-Leu-Arg (SEQ ID NO: ),Leu-Leu-Gly-Pro-Gly-Arg-Pro-Tyr-Arg (SEQ ID NO: ),Val-Met-Gly-Thr-Leu-Val-Ala-Leu-Val (SEQ ID NO ),Leu-Leu-Ala-Val-Leu-Tyr-Cys-Leu (SEQ ID NO: ),Ala-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val (SEQ ID NO: ),Glu-Ala-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val (SEQ ID NO: ),Ala-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val (SEQ ID NO: ),Ile-Leu-Thr-Val-Ile-Leu-Gly-Val-Leu (SEQ ID NO: ),Ile-Met-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: ),Ile-Thr-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: );Thr-Ile-Thr-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: ),Tyr-Leu-Glu-Pro-Gly-Val-Thr-Val (SEQ ID NO: ),Tyr-Leu-Glu-Pro-Gly-Val-Thr-Val-Ala (SEQ ID NO: ),Lys-Thr-Trp-Gly-Gln-Tyr-Trp-Gln-Val (SEQ ID NO: ),Lys-Thr-Trp-Gly-Gln-Tyr-Trp-Gln-Val-Leu (SEQ ID NO: ),Val-Leu-Lys-Arg-Cys-Leu-Leu-His-Leu (SEQ ID NO: ),Leu-Asn-Val-Ser-Leu-Ala-Asp-Thr-Asn (SEQ ID NO: ),Ser-Leu-Ala-Asp-Thr-Asn-Ser-Leu-Ala-Val (SEQ ID NO: ),Leu-Leu-Asp-Gly-Thr-Ala-Thr-Leu-Arg-Leu (SEQ ID NO; ),Val-Leu-Tyr-Arg-Tyr-Gly-Ser-Phe-Ser-Val (SEQ ID NO: ),Ala-Leu-Asp-Gly-Gly-Asn-Lys-His-Phe-Leu (SEQ ID NO: ),Val-Leu-Pro-Ser-Pro-Ala-Cys-Gln-Leu-Val (SEQ ID NO: ),Ala-Leu-Glu-Ala-GIn-Gln-Glu-Ala-Leu (SEQ ID NO: ),Ile-Leu-Glu-Ser-Leu-Phe-Arg-Ala-Val (SEQ ID NO: ),Ser-Leu-His-Cys-Lys-Pro-Glu-Glu-Ala-Leu (SEQ ID NO: ),Pro-Leu-Val-Leu-Gly-Thr-Leu-Glu-Glu-Val (SEQ ID NO: ),Cys-Leu-Gly-Leu-Ser-Tyr-Asp-Gly-Leu (SEQ ID NO: ),Cys-Leu-Gly-Leu-Ser-Tyr-Asp-Gly-Leu-Leu (SEQ ID NO: ),Leu-Leu-Lys-Tyr-Arg-Ala-Arg-Glu-Pro-Val (SEQ ID NO: ),Phe-Leu-Trp-Gly-Pro-Arg-Ala-Leu-Val (SEQ ID NO: ),Glu-Ala-Asp-Pro-Thr-Gly-His-Ser-Tyr (SEQ ID NO: ),Ser-Leu-Asp-Asp-Tyr-Asn-His-Leu-Val (SEQ ID NO: ),Thr-Leu-Asp-Ser-Gln-Val-Met-Ser-Leu (SEQ ID NO: ),Val-Met-Gly-Thr-Leu-Val-Ala-Leu-Val (SEQ ID NO: ) and epitope-containingfragments thereof.
 3. The method of claim 1 wherein the heat shockprotein is selected from the group consisting of hsp70, hsp90, gp96,BiP, hsp40, hsp170 and mixtures thereof.
 4. The method of claim 2wherein the heat shock protein is selected from the group consisting ofhsp70, hsp90, gp96, BiP, hsp40, hsp170 and mixtures thereof.
 5. Themethod of claim 1 wherein the melanoma antigen is covalently joined toone or more javelin molecule selected from the group consisting ofpeptides having the sequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ IDNO: ), Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ) and combinationsthereof.
 6. The method of claim 5 wherein the javelin molecule is joinedto the melanoma antigen by a peptide linker.
 7. The method of claim 2wherein the melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ) and combinations thereof.8. The method of claim 7 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 9. The method of claim 3 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ) and combinations thereof.10. The method of claim 9 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 11. The method of claim 4 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ) and combinations thereof.12. The method of claim 11 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 13. The method of claim 1 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences Phe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ) and combinations thereof.14. The method of claim 13 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 15. The method of claim 2 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences Phe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ) and combinations thereof.16. The method of claim 15 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 17. The method of claim 3 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences Phe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ) and combinations thereof.18. The method of claim 17 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 19. The method of claim 4 whereinthe melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences Phe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ) and combinations thereof.20. The method of claim 19 wherein the javelin molecule is joined to themelanoma antigen by a peptide linker.
 21. The method of claim 1 whereinthe immunotherapeutic compositions comprises (a) a first melanomaantigen comprising a peptide having the sequenceTyr-Met-Asp-Gly-Thr-Met-Ser-Gln-Val (SEQ ID NO: ) covalently linked to afirst javelin molecule and (b) a second melanoma antigen comprising apeptide having the sequence Ile-Met-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ IDNO: ) linked to a second javelin molecule.
 22. The method of claim 21wherein the first and second javelin molecules are the same and comprisea peptide having the sequence His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ IDNO: ) and wherein the heat shock protein is hsp70.
 23. Animmunotherapeutic composition comprising a heat shock protein and amelanoma antigen, wherein the melanoma antigen is selected from thegroup consisting of tyrosinase, tyrosinase related protein 1, tyrosinaserelated protein 2, gp100, MAGE antigens, BAGE antigens, NYES01, MARTantigens, GM2, antigenic portions thereof and combinations thereof,wherein the melanoma antigen is covalently bound to a javelin molecule,and wherein the melanoma antigen bound to the javelin molecule isnon-covalently bound to the heat shock protein.
 24. Theimmunotherapeutic composition of claim 23 wherein the melanoma antigenis selected from the group consisting of peptides having the sequencesTyr-Met-Asp-Gly-Thr-Met-Ser-Gln-Val (SEQ ID NO: ),Tyr-Met-Asn-Gly-Thr-Met-Ser-Gln-Val (SEQ ID NO: ),Met-Leu-Leu-Ala-Val-Leu-Tyr-Val-Leu (SEQ ID NO: ),Met-Ser-Leu-Gln-Arg-Gln-Phe-Leu-Arg (SEQ ID NO: ),Leu-Leu-Gly-Pro-Gly-Arg-Pro-Tyr-Arg (SEQ ID NO: ),Val-Met-Gly-Thr-Leu-Val-Ala-Leu-Val (SEQ ID NO ),Leu-Leu-Ala-Val-Leu-Tyr-Cys-Leu (SEQ ID NO: ),Ala-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val (SEQ ID NO: ),Glu-Ala-Ala-Gly-Ile-Gly-Ile-Leu-Thr-Val (SEQ ID NO: ), Ala-Ala-Gly-IleGly-Ile-Leu-Thr-Val (SEQ ID NO: ), Ile-Leu-Thr-Val-Ile-Leu-Gly-Val-Leu(SEQ ID NO: ), Ile-Met-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: ),Ile-Thr-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: ),Thr-Ile-Thr-Asp-Gln-Val-Pro-Phe-Ser-Val (SEQ ID NO: ),Tyr-Leu-Glu-Pro-Gly-Val-Thr-Val (SEQ ID NO: ),Tyr-Leu-Glu-Pro-Gly-Val-Thr-Val-Ala (SEQ ID NO: ),Lys-Thr-Trp-Gly-Gln-Tyr-Trp-Gln-Val (SEQ ID NO: ),Lys-Thr-Trp-Gly-Gin-Tyr-Trp-Gln-Val-Leu (SEQ ID NO: ),Val-Leu-Lys-Arg-Cys-Leu-Leu-His-Leu (SEQ ID NO: ),Leu-Asn-Val-Ser-Leu-Ala-Asp-Thr-Asn (SEQ ID NO: ),Ser-Leu-Ala-Asp-Thr-Asn-Ser-Leu-Ala-Val (SEQ ID NO: ),Leu-Leu-Asp-Gly-Thr-Ala-Thr-Leu-Arg-Leu (SEQ ID NO; ),Val-Leu-Tyr-Arg-Tyr-Gly-Ser-Phe-Ser-Val (SEQ ID NO: ),Ala-Leu-Asp-Gly-Gly-Asn-Lys-His-Phe-Leu (SEQ ID NO: ),Val-Leu-Pro-Ser-Pro-Ala-Cys-Gln-Leu-Val (SEQ ID NO: ),Ala-Leu-Glu-Ala-Gln-Gln-Glu-Ala-Leu (SEQ ID NO: ),Ile-Leu-Glu-Ser-Leu-Phe-Arg-Ala-Val (SEQ ID NO: ),Ser-Leu-His-Cys-Lys-Pro-Glu-Glu-Ala-Leu (SEQ ID NO: ),Pro-Leu-Val-Leu-Gly-Thr-Leu-Glu-Glu-Val (SEQ ID NO: ),Cys-Leu-Gly-Leu-Ser-Tyr-Asp-Gly-Leu (SEQ ID NO: ),Cys-Leu-Gly-Leu-Ser-Tyr-Asp-Gly-Leu-Leu (SEQ ID NO: ),Leu-Leu-Lys-Tyr-Arg-Ala-Arg-Glu-Pro-Val (SEQ ID NO: ),Phe-Leu-Trp-Gly-Pro-Arg-Ala-Leu-Val (SEQ ID NO: ),Glu-Ala-Asp-Pro-Thr-Gly-His-Ser-Tyr (SEQ ID NO: ),Ser-Leu-Asp-Asp-Tyr-Asn-His-Leu-Val (SEQ ID NO: ),Thr-Leu-Asp-Ser-Gln-Val-Met-Ser-Leu (SEQ ID NO: ) andVal-Met-Gly-Thr-Leu-Val-Ala-Leu-Val (SEQ ID NO: ) and epitope-containingfragments thereof.
 25. The immunotherapeutic composition of claim 23wherein the heat shock protein is selected from the group consisting ofhsp70, hsp90, gp96, BiP, hsp40, hsp 170 and mixtures thereof.
 26. Theimmunotherapeutic composition of claim 24 wherein the heat shock proteinis selected from the group consisting of hsp70, hsp90, gp96, BiP, hsp40,hsp 170 and mixtures thereof.
 27. The immunotherapeutic composition ofclaim 23 wherein the melanoma antigen is covalently joined to one ormore javelin molecule selected from the group consisting of peptideshaving the sequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO:______), Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ______ andcombinations thereof.
 28. The immunotherapeutic composition of claim 27wherein the javelin molecule is joined to the melanoma antigen by apeptide linker.
 29. The immunotherapeutic composition of claim 24wherein the melanoma antigen is covalently joined to one or more javelinmolecule selected from the group consisting of peptides having thesequences His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ______),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ______) and combinationsthereof.
 30. The immunotherapeutic composition of claim 29 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.31. The immunotherapeutic composition of claim 25 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesHis-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ______),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ______) and combinationsthereof.
 32. The immunotherapeutic composition of claim 31 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.33. The immunotherapeutic composition of claim 26 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesHis-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO: ______),Trp-Pro-Trp-Ala-Phe-Asp-Trp-His (SEQ ID NO: ______) and combinationsthereof.
 34. The immunotherapeutic composition of claim 33 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.35. The immunotherapeutic composition of claim 23 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesPhe-Trp-Gly-Leu-Trp-Pro-Trp-Glu. (SEQ ID NO: ______),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ______) and combinationsthereof.
 36. The immunotherapeutic composition of claim 35 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.37. The immunotherapeutic composition of claim 24 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesPhe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ______),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ______) and combinationsthereof.
 38. The immunotherapeutic composition of claim 37 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.39. The immunotherapeutic composition of claim 25 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesPhe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ______),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ______) and combinationsThereof.
 40. The immunotherapeutic composition of claim 39 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.41. The immunotherapeutic composition of claim 26 wherein the melanomaantigen is covalently joined to one or more javelin molecule selectedfrom the group consisting of peptides having the sequencesPhe-Trp-Gly-Leu-Trp-Pro-Trp-Glu (SEQ ID NO: ______),Glu-Trp-Pro-Trp-Leu-Gly-Trp-Phe (SEQ ID NO: ______) and combinationsthereof.
 42. The immunotherapeutic composition of claim 41 wherein thejavelin molecule is joined to the melanoma antigen by a peptide linker.43. The immunotherapeutic composition of claim 23 comprising a first anda second melanoma antigen, wherein the first melanoma antigen comprisesa peptide having the sequence Tyr-Met-Asp-Gly-Thr-Met-Ser-Gln-Val (SEQID NO: ) and is linked to a javelin molecule, and the compositionfurther comprises a second melanoma antigen linked to a javelinmolecule.
 44. The immunotherapeutic composition of claim 43 wherein thesecond melanoma antigen comprises a peptide having the sequenceIle-Met-Asp-Gln-Val-Pro-Phe-Ser-Val.
 44. The immunotherapeuticcomposition of claim 43 wherein the first and second melanoma antigensare linked to the same species of javelin molecule, which comprises apeptide having the sequence His-Trp-Asp-Phe-Ala-Trp-Pro-Trp (SEQ ID NO:) and wherein the heat shock protein is hsp70.